Journal of Biotechnology 349 (2022) 32–46

Contents lists available at ScienceDirect

Journal of Biotechnology
journal homepage: www.elsevier.com/locate/jbiotec

Microalgal drugs: A promising therapeutic reserve for the future

Ankesh Ahirwar a, 1, Khushboo Kesharwani b, 1, Rahul Deka a, 1, Shreya Muthukumar a, 1,
Mohd. Jahir Khan a, Anshuman Rai c, Vandana Vinayak a, *, Sunita Varjani d, *,
Khashti Ballabh Joshi b, Shruti Morjaria a
a
Diatom Nanoengineering and Metabolism Laboratory (DNM), School of Applied Science, Dr. Harisingh Gour Central University, Sagar, Madhya Pradesh 470003, India
b
Department of Chemistry, Dr. Harisingh Gour Central University, Sagar, Madhya Pradesh 470003, India
c
MMU, Deemed University, School of Engineering, Department of Biotechnology, Ambala, Haryana, 133203, India
d
Gujarat Pollution Control Board, Gandhinagar, Gujarat 382 010, India

A R T I C L E I N F O A B S T R A C T

Keywords: Over the decades, a variety of chemically synthesized drugs are being used to cure existing diseases but often
Algae these drugs could not be effectively employed for the treatment of serious and newly emerging diseases.
Diseases Fortunately, in nature there occurs immense treasure of plants and microorganisms which are living jewels with
Drugs
respect to their richness of medically important metabolites of high value. Hence, amongst the existing micro­
SARS-CoV-2
Sulphur polysaccharides
organism(s), the marine world offers a plethora of biological entities that can contribute to alleviate numerous
Treatment human ailments. Algae are one such photosynthetic microorganism found in both marine as well as fresh water
which are rich source of metabolites known for their nutrient content and health benefits. Various algal species
like Haematococcus, Diatoms, Griffithsia, Chlorella, Spirulina, Ulva, etc. have been identified and isolated to pro­
duce biologically active and pharmaceutically important high value compounds like astaxanthin, fucoxanthin,
sulphur polysaccharides mainly galactose, rhamnose, xylose, fucose etc., which show antimicrobial, antifungal,
anti-cancer, and antiviral activities. However, the production of either of these bio compounds is favored under
conditions of stress. This review gives detailed information on various nutraceutical metabolites extracted from
algae. Additionally focus has been made on the role of these bio compounds extracted from algae especially
sulphur polysaccharides to treat several diseases with prospective treatment for SARS-CoV-2. Lastly it covers the
knowledge gaps and future perspectives in this area of research.

1. Introduction
Rise in population and industrialization has manifested human
interference widely across the globe (Ajibade et al., 2021). This has led
to anthropogenic pollution and has not spared even the most pristine
sights like Antarctica (Pino-Cortés et al., 2021). Among the different
effluents effecting the quality of our globe, pollutants in water change
the biodiversity of microorganisms and the interconnected food chain
which includes aquatic flora and fauna (Khan et al., 2020). The pollut­
ants like heavy metals, dyes, hydrocarbons hinder growth of microor­
ganisms thus effecting their phylogenetic diversity (Mishra et al., 2019;
Devda et al., 2021; Varjani et al., 2021). This leads to outbreak of
various diseases which opens a plethora of drug testing and experi­
mentation. Even though mankind has synthesized a variety of drugs and
medicines but the real treasure of treating all the existing and
non-existing diseases lies in the secondary metabolites being synthesized
by photosynthetic algae in the depth of the sea (Chia et al., 2021). Algae
are eukaryotic plants that evolved on earth around one billion years ago
and comprised the major photosynthetic organisms belonging to
kingdom Protista (Nagarajan et al., 2021)(Chapman, 2013). There are
over a million species of algae found on earth today and many more to be
discovered and classified (Guiry, 2012). Based on their size, algae are
broadly classified into macroalgae also called as seaweeds that are
multicellular and microalgae that are unicellular. Besides maintaining
the earth’s CO2 levels and preventing global warming, algae are
generous source of proteins and dietary fibers that can be used as
anti-inflammatories, anti-microbials and for disease prevention (Wells
et al., 2017). They thus have opened an arena of food supplements that

* Corresponding authors.
E-mail addresses: kapilvinayak@gmail.com, vvinayak@dhsgsu.edu.in (V. Vinayak), drsvs18@gmail.com (S. Varjani).
1
Authors contributed equally.

https://doi.org/10.1016/j.jbiotec.2022.03.012
Received 20 December 2021; Received in revised form 17 February 2022; Accepted 20 March 2022
Available online 25 March 2022
0168-1656/© 2022 Elsevier B.V. All rights reserved.
A. Ahirwar et al.
come under the umbrella of nutraceuticals. Almost all microalgae
contain polyunsaturated fatty acids (PUFAs) called eicosapentaenoic
acid and docosahexaenoic acid which are the two most important
omega-3-fatty acids exclusive to them (Barkia et al., 2019). These
compounds are referred to as wonder molecules since they are avowed
to reduce the risk of cardiac diseases. In view of the phenomenal nu­
traceutical properties of microalgae, world health organization (WHO)
has declared Spirulina as one of the illustrious “superfoods” globally
(Chakdar and Pabbi, 2017). Therefore, it is only natural that mankind
traverses the vast oceans that covers over 70% of the planet in order to
cash in the innumerable benefits of this remarkable organism, not only
as food but also for the multifarious useful compounds that it has to
offer. However, change in the marine environment due to release of
waste in the waterbodies and climate change have jeopardized the ex­
istence of both microalgae and macroalgae (Brodie et al., 2009). This
will have grave implications on the marine ecosystem and the planet.
Henceforth there is a dire need to identify and conserve these organisms
before it is too late, otherwise humanity would not be privy to so many
benefits that the ocean’s most primeval organisms have to confer. Since
the main characteristic feature of algae is the presence of chloroplasts
with which they are able to carry out the process of photosynthesis
(Vecchi et al., 2020). They aren’t dependent on other organisms for
nutrition since it has the capability of carrying out photosynthesis by its
own. The microalgae have abundant deposition of chemical substances
in their cell walls making it thick and resilient from environment
changes, thus making them survive easily in harsh conditions (Ahirwar
et al., 2021a; D’Silva et al., 2012). On the other hand, algae are not only
useful for humans in fact it is beneficial for our ecosystem. This is
essentially due to the fact that algae are important class of algae which
resides mainly in aquatic environments such as marine and freshwater
bodies including wastewaters (Khan et al., 2021; Nguyen et al., 2021;
Saravanan et al., 2021).
Since early 1950s there has been an elevated interest in exploiting
marine organisms for novel drugs (Laurienzo, 2010). It has been
observed that among the red, green and brown algae, the red algae offer
the greatest number of bioactive compounds like polysaccharides
(alginate, agar, and carrageenan), lipids, polyphenols, steroids, glyco­
sides, flavonoids, tannins, saponins, alkaloids, triterpenoids, anthra­
quinones and cardiac glycosides that can be used as potential
therapeutics (Aziz et al., 2020; Banerjee et al., 2018). One of the pivotal
advantages of deriving marine drugs from microalgae is their metabolic
plasticity that can be exploited to set off the production of pharmaco­
logically important metabolites and can be cultivated using
photo-bioreactors for large-scale production (Martínez Andrade et al.,
2018).
Algae-derived compounds are also potential antimicrobials, for e.g.
species of Chlorella, Nostoc and certain brown algae have known to have
antimicrobial activity against food borne pathogens like Staphylococcus
aureus and Bacillus subtilis along with being food supplements
(Pina-Pérez et al., 2017). Literature reports also revealed the human
consumption of algae owing to its beneficial role in human’s daily life as
they are rich source of fibers, minerals, antioxidants, vitamins, pig­
ments, steroids, lectins, halogenated compounds, polysaccharides, pro­
teins, polyunsaturated fatty acids and other lipids (Parsaeimehr and
Chen, 2013). Due to its biologically active potential properties, it has
been used since ages and will be used up to ages. It is thus a source of
extracting many natural products for pharmacological advantages such
as antibacterials, antimicrobials (Pina-Pérez et al., 2017), antivirals,
therapeutic proteins, anticancer (Tewari et al., 2019), antifungals and
many more (Jain et al., 2020). Additionally, polysaccharides the vital
components from algae are of utmost importance as therapeutics espe­
cially as antivirals. It has been observed that microalgae Gymnodinium
impudicum, Porphyridium cruentum, Cochlodinium polykrikoides rich in
sulphur polysaccharides are identified to have anti-viral activities
against encephalomyocarditis virus, influenza A virus (Flu-A), Herpes
simplex virus (HSV-1 and HSV-2), hepatitis B virus (HBV), viral
33
Journal of Biotechnology 349 (2022) 32–46
haemorrhagic septicaemia virus (VHSV), African swine fever virus
(ASFV), measles virus, mumps virus, HIV-1 (Freitas et al., 2021; Kiran
and Venkata Mohan, 2021).
On the offset microalgae (diatoms) which are the most diverse and
abundant besides containing most of the therapeutic components
(Malviya et al., 2016); they have a distinct siliceous cell wall that is
luring scientists into jockeying these organisms into potential drug de­
livery systems too (Aw et al., 2011). No doubt, they lead existing
microalgae and rainforests in fixing 25% of atmospheric CO2 and pro­
duce around 20% of the earth’s oxygen (Chew et al., 2021; Pierella
Karlusich et al., 2021). Notwithstanding this they are can grow even in
diverse conditions and have many applications such as metabolic engi­
neering (Huang and Daboussi, 2017; Vinayak et al., 2021a), biofuels
(Graham et al., 2012), bio indicators for sensing environmental condi­
tions (Gautam et al., 2017; Khan et al., 2020; Rivera-Rondón and
Catalan, 2020), forensic science (Vinayak, 2020; Vinayak and Gautam,
2019), value added products utilizing wastewater (Khan et al., 2021;
Vinayak et al., 2021b), drug vector (Singh et al., 2020), in nanotech­
nology (Gupta et al., 2018), drugs (Hussein and Abdullah, 2020) and as
drug vectors (Kabir et al., 2020).
Hence, the engineering of algae to get value-added compounds from
potential microalgae is very important to maintain a healthy ecosystem
not only for humans but also for our surrounding flora and fauna. Many
times, mankind has witnessed the outbreak of diseases which are un­
known in their origin and cause. This has thus led to a trial of drug
testing which takes a due course of time for its positive outcome which is
well witnessed in SARS-CoV-2 era. The effectiveness and novel mode of
action of these algal metabolites against SARS-CoV-2 is crucial aspect
together with an emphasis on the new emerging diseases and their
treatment using several metabolites which are naturally biosynthesized
by various algal species. The outbreak of COVID-19 pandemic has
emphasized the vital need for antiviral and immunity promoter sub­
stances that can be rapidly deployed when a previously unidentified or
overlooked virus unexpectedly becomes a global emergency (Ray et al.,
2022).
Researchers are firmed that algal metabolites could be utilized in an
entirely different manner in potential medical preparations as they are
having the broad range of mechanisms against viruses, economical, less
toxic and broad acceptability. Thus, the therapeutic drugs from algal
metabolites which subsist on sunlight and CO2 in the air might be
manufactured and can be scaled up at lower capital cost. Henceforth
algae can be a supreme and cost-effective substitute of synthetic drugs.
Once medically tested safe, being biogenic and biocompatible, the algal
polysaccharide and other metabolites based antiviral drugs will attract
the attention of pharmaceutical industry in search of novel treatment of
serious diseases. (Geetha Bai and Tuvikene, 2021).
We reviewed the current status of algal metabolite from microalgae
such as carotenoids (astaxanthin), polysaccharide (spirulan), proteins
(lectins, cyanovirin-N, scytovirin, microvirin), lipids, vitamins, etc. as
well as macroalgal proteins like griffithsin, carrageenans, fucoidans,
ulvan, diterpenes as natural high value potential preventive agent due to
their antioxidant, anti-inflammatory, anticancer, neuroprotective and
anticoagulative properties (Sanjeewa and Jeon, 2021). This review also
focuses on naturally biosynthesizing marine drugs from algal commu­
nities and their implication against pathogens conferring antibacterial,
antiviral and antifungal properties. A special emphasis has been laid
onto the present SARS-CoV-2 pandemic in the formulation of potent
antiviral compounds from algae to target SARS-CoV-2. It also empha­
sizes on roadblocks and perspectives for future research in analyzing
algal compounds and testing them against existing and possibly incur­
able ailments.
2. Algal metabolites
The varied forms of marine algae, can be used as food, medicines
(Raja et al., 2013), dietary supplements (Ścieszka and Klewicka, 2019)
A. Ahirwar et al. Journal of Biotechnology 349 (2022) 32–46

and also in drugs nano formulations (Pina-Pérez et al., 2017). Marine
algae have potential to withstand synthetic drugs and had been
receiving great attention, as it is a source of bioactive metabolites in
drug industries (Aditya et al., 2016; Jain et al., 2020; Shannon and
Abu-Ghannam, 2016). On the other hand, edible form of marine algae
mainly include high value compounds like carotenoids and pigments
(Vinayak et al., 2015). One such example is that of astaxanthin from
green algae green microalgae Neochloris wimmeri, Protosiphon botryoides
and Scotiellopsis oocystiformis, fungi (Xanthophyllomyces dendrorhous)
(also known as Phaffia) and even yeasts (Barredo et al., 2017), but
mainly from Haematococcus pluvialis which comes under the class of
carotenoid metabolites with exceptional antioxidant properties(Ahirwar
et al., 2021b). This makes it widely accepted as a health supplement for
humans with its market value reaching 3.4 billion USD (Mehta et al.,
2018). Besides this diatoms like Phaeodactylum tricornutum is another
good examples of such algae which are rich source of bioactive metab­
olites such as carotenoids like xanthophylls; β carotene, fucoxanthin,
zeaxanthin, phycocyanin, flavonoid, fatty acids and omega − 3 PUFA
(polyunsaturated fatty acids) found in diatom Nitzschia sp.(Saranya and
Ramachandra, 2021). On the other hand, marine macroalgae or sea­
weeds naturally biosynthesize carrageenans which is a sulphated poly­
saccharides composed of fucoidan, fucosterol, sodium alginate and
protein; griffithsin. Not limiting to this, the most widely accepted
vitamin rich supplement in the market named Spirulina is extracted from
the algae, Spirulina platensis (Grosshagauer et al., 2020).
Additionally, cyanovirin, scytovirin and microvirin can be isolated
from blue green algae or cyanobacteria. These metabolites involve
treatment of various diseases having antiviral, antibacterial and anti­
fungal properties or other kinds of metabolites biosynthesized by algae
as seen in Table 1 (Pereira et al., 2021; Sekar et al., 2021). Thus these
algal metabolites have become a crucial topic of research in medicine,
nutraceutical industry, cosmetic industry, biofuel production and many
other useful sectors for mankind (Rathna et al., 2019; Singh et al.,
2017a). The research leap from synthetic to natural sources for potent
pharmacological activities against disease causing organisms has been
thus the central goal of researchers all over the globe. In the subsequent
sections, the diverse algal metabolites from various types of algal species
are briefly discussed.
2.1. Microalgae
2.1.1. Polysaccharides
Microalgae are rich in carbohydrates such as glucose and starch
which helps in facilitating various biological functions of the algae. They
form the basis of energy generation in most of the living organisms and
are considered as long-chain carbohydrates which form the complex
structures of plant and exoskeletons of arthropod species (Zhao et al.,
2019). These antiviral polymers have high sulfation level and are

Table 1
Metabolites produced by algae for a wide range of treatment modalities.
Algae Class of Algae Type of Metabolite Used in Treatment References

Microalgae
Scytonemavarium Cyanophyceae Scytovirin Ebola virus (Siqueira et al., 2017b)
Spirulina platensis Cyanophyceae Spirulan HsV-1 infection (Le et al., 2020)
Spirulina platensis Cyanophyceae β-carotene and phycocyanin Reduction in expression of TNF-α and IL-6 (Wu et al., 2016)
Synechocystis spp. Cyanophyceae Fatty acids and phenols Growth inhibition of bacteria, E. coli S. aureus (Rojas et al., 2020)
Macroalgae
Ulva fasciata Chlorophyceae Guaiane sesquiterpene Inhibit kinase site of EGFR expressed in breast cancer cell line (Gutiérrez-Rodríguez et al.,
2018)
Kjelmaniella crassifolia Chlorophyceae Fucoidan Influenza A virus (Wang et al., 2017)
Canistrocarpus Phaeophyceae Diterpene Herpes simplex virus (de Souza Barros et al., 2017)
cervicornis
Nannochloropsis oculata Eustigmatophyceae Zeaxanthin Inhibit excess melanin formation (Pangestuti et al., 2020)
Ascophyllum nodosum Phaeophyceae Ascophyllan Skin cancer (Abu et al., 2015)
Bifurcariabifurcata Phaeophyceae Eleganonal Free radical scavenging (Silva et al., 2019)
Cystoseira foeniculacea Phaeophyceae Polyphenol Free radical scavenging (Messina et al., 2019)
Sargassum hemiphyllum Phaeophyceae Sulphated polysaccharide Inflammation of Macrophages (Jayawardena et al., 2020)
Ecklonia cava Phaeophyceae Phlorotannin Reactive oxygen species scavenging (Shrestha et al., 2021)
Ecklonia kurome Phaeophyceae Phlorotannin Inhibition of phospholipid peroxidation (Sugiura et al., 2021)
Ecklonia cava Phaeophyceae Dieckol Inhibition of α-Glucosidase inhibitor; PTP 1B (Sharifuddin et al., 2015)
Ecklonia stolonifera Phaeophyceae Polyphenols Inhibition of α-Glucosidase inhibitor; PTP 1B (Ezzat et al., 2018)
Ecklonia bicyclis Phaeophyceae Eckol Inhibition of α-Glucosidase inhibitor; PTP 1B (Wan-Loy and Siew-Moi,
2016)
Pelvetia siliquosa Phaeophyceae Fucosterol Inhibition of sorbitol and glucose accumulation in (Pradhan et al., 2021)
Sprague–Dawley diabetic rats
Laminaria angustata Phaeophyceae Sodium alginate Inhibition of rising blood glucose and insulin levels in Wistar (Pradhan et al., 2021)
rats
Sargassum serratifolium Phaeophyceae Sargahydroquinoic acid Inhibition of ACE, PTB 1B (Ali et al., 2017)
Undaria pinnatifida Phaeophyceae Omega-3 PUFA (DHA and Allergic reactions (Tanna and Mishra, 2018)
EPA)
Sargassum binderi Phaeophyceae Fucosterol Reduction of apoptosis and Sub-G1 cell populations (Fernando et al., 2019)
Sargassum horneri Phaeophyceae Chromene Inhibition of mRNA expression, CD4 and CD8 population, IgE (Herath et al., 2020)
expression
Cladosiphon okamuranus Phaeophyceae Fucoxanthin Free radical scavenging (Boominathan and Mahesh,
2015)
Fucus vesiculosus Phaeophyceae Oxidation of Macrophages (Barbosa et al., 2017)
Sargassum horneri Phaeophyceae Flavonoid Inhibition of pro-inflammatory Cytokines, upregulated mRNA, (Herath et al., 2020)
toll-like receptors
Undaria pinnatifida Phaeophyceae Fucoidan H1N1 infection (Richards et al., 2020)
Fucus evanescens Phaeophyceae Fucoidan Herpes simplex virus-2 (Krylova et al., 2020)
Red seaweed Rhodophyceae Carrageenan Common Cold, Anti-herpes simplex virus (Ana et al., 2021)
Griffithsia sp. Rhodophyceae Griffithsin Japanese encephalitis (Rosa et al., 2020)
Rhodomela confervoides Rhodophyceae HPN analogues Inhibition of PTP 1B (Rayapu et al., 2021)
Gracilariopsis Rhodophyceae Sulphated polysaccharide Free radical scavenging (Cao et al., 2019)
lemaneiformis

34
A. Ahirwar et al.
negatively charged; therefore, they are also termed as sulfated poly­
saccharide (SPS). Algal polysaccharides perform antiviral mechanism by
the inhibition of virus action, enhance the immunity of the host against
viral infection, virus internalization and in some cases only binding of
polysaccharides can inhibit the virus activity directly (Shi et al., 2017).
Other ways of antiviral mechanism of algal polysaccharides are inhibi­
tion of virus transcription and replication, involving direct action of
sulfated polysaccharides along with viral replication enzymes (Fig. 1).
Virus infection can take place by few steps which are attachment to host
cells, penetration, uncoating, replication, assembly and release. Algal
polysaccharides can stop the activity of the virus at any of the stage due
to their structural and chemical compositional properties as well as
preferred mode of anti-viral action (Geetha Bai and Tuvikene, 2021;
Hans et al., 2021). Several algal derived sulfated polysaccharides such as
sea cucumber sulfated polysaccharide have been reported with inhibi­
tory action against SARSCoV-2. Noteworthy antiviral activities are
showed by sea cucumber sulfated polysaccharide, carrageenan and
fucoidan at concentrations of 3.90–500 µg/mL. Sea cucumber sulfated
polysaccharide showed the best inhibitory activity with half-maximal
inhibitory concentration of 9.10 µg/mL (Song et al., 2020).
The cell wall of algae is made up of complex natural biopolymers
(Hans et al., 2021). On the offset, the presence of polysaccharides in the
cell wall makes the algal cell rigid, thus resisting its easy breakdown and
lysis making the harvesting of biocompounds a cost effective procedure
(Ahirwar et al., 2021a). They are composed of carbon, hydrogen, oxy­
gen, nitrogen, sulphur, phosphorus etc. and can be classified into mac­
robiomolecule and microbiomolecule depending on their size. Among
the important components extracellular polymeric substances (EPS) are
important class of polysaccharides excreted by algae (Khan et al., 2020).
EPS are natural polymers compound mixture of macromolecular poly­
electrolytes comprised of polysaccharides, proteins, lipids, amino,
aliphatic, aromatics group etc (Decho and Gutierrez, 2017). They are
metabolites which in turn provide the stability to the live algal cells and
protect the later from the harsh and unfavorable external environments
(Seedevi et al., 2017). They however, vary in terms of its chemical na­
ture and its distribution.
Fig. 1. Mechanism of polysaccharide produced from microalgae causing inhibition to attachment of virus to host cell and its further transcription.
35
Journal of Biotechnology 349 (2022) 32–46
The major difference that lies with cell wall of marine algae and that
of a plant cell wall is the deposition of sulphated polysaccharides in the
former (García-Vaquero et al., 2017). Sulphated polysaccharides have
been widely investigated for their nutraceutical and medicinal values
(Udayangani et al., 2020). On the basis of chemical nature, algal poly­
saccharides are classified into sulfuric acid polysaccharides, sulfated
xylan moieties and galactans (Arlov et al., 2021). On the offset, the
important polysaccharides distributed across the algae class, phaeo­
phyceae include alginic acid, laminarin, sargassan and fucoidan
(Setyorini and Puspitasari, 2021). Besides the microalgae, brown sea­
weeds also contain wide range of polysaccharides such as fucoidans and
several other sulphated polysaccharides in varying proportions having
antiviral, antibacterial and antifungal properties (Alam et al., 2021;
Pagarete et al., 2021) as shown in Fig. 2.
2.1.2. Different components lipids and their properties
Lipids are generally considered as non-water-soluble, biologically
important macrobiomolecule. They provide definite structure, help in
signaling pathways and also help in storing reserve energy (Muro et al.,
2014)(Maurya M. et al., 2021). Lipids are low value compounds which
are present in various forms such as fatty acids, sterols, glycerides,
fat-soluble vitamins and phospholipids. The lipid content of algae is
classified into two parts; one being the cell membrane-based lipids such
as glycosylglycerides, phosphoglycerides and other one being the energy
storage-based lipids such as triacyclglycerol (Krishnan et al., 2021).
Other than this the two conventional sources of lipids viz; sphingolipids
and sterols are also present in varying proportions (Stonik and Stonik,
2018). Diatoms and Euglena sp. also contain traces of unconventional
lipids such as phosphatidyl sulphocholine (Li-Beisson et al., 2019;
Vinayak et al., 2014). Similarly, Botryococcus braunii and other marine
algae contain traces of novel hydrocarbons and lipids such as haloge­
nated fatty acids(Kartik et al., 2021). Fatty acids play a major role in
maintaining the stability of membranes along with proper organization
of cells in the human body (Maulucci et al., 2016). Unfavorable condi­
tions manifest the production and release of fatty acids from algal cells
in order to counter act the action of pathogenic microbes that cause loss
A. Ahirwar et al.
Fig. 2. Marine Algae: Useful extracts, medicinal use and possible application field.
in cell integrity. Reports suggests that carbon unsaturation in the fatty
acid structure directly correlates with the efficient antibacterial property
of the algae (Cepas et al., 2021). The intricate organization of fatty acids
and lipids as a whole contributes to its diversified efficiency in thera­
peutics hall of fame (Zhang and Liu, 2017).
Both microalgae and macroalgae thus are capable of synthesizing a
therapeutically relevant class of fatty acids that is the polyunsaturated
fatty acids or PUFAs (Pohl and Zurheide, 2019). PUFAs play a major role
in lowering down the complications of cardiovascular diseases and with
the incapability of humans in the synthesizing PUFAs, the role of algae
becomes very vital (Harwood, 2019). Typically, health and dietary
supplements, omega-3 and omega-6 fatty acids account for the main and
major composition of algal PUFAs (Saini and Keum, 2018). However,
there distribution varies from species to species.
It has been seen that both Rhodophyceae and Phaeophyceae classes
of algae contribute to a high amount of extractable omega-3 as well as
omega-6 fatty acids (Widyaswari and Amir, 2021). It was observed that
lipid profiling of Chlorella vulgaris showed varying proportions of fatty
acids such as oleic acids, linolenic and palmitic acids (Siahbalaei et al.,
2021). Similarly, short length fatty acids were obtained from Haemato­
coccus pluvialis (Butler et al., 2020). Likewise, an omega-3 PUFA namely,
stearic acid was successfully extracted from an edible seaweed from
kelps, Undaria pinnatifida (Dellatorre et al., 2020). Fatty acids such as
palmitic acid, myristic acid, oleic acid and others were found to be
present in lipid extract of Cladophora rupestris as analyzed using gas
chromatography (Munir et al., 2019).
Sterols are yet another category of lipids having an amphipathic
nature extracted from algae quite extensively. Sterols are considered as
subset of steroids having a polar hydroxyl group in the third position of
the flat A-ring structure. They are generated by the HMG-CoA (3-
36
Journal of Biotechnology 349 (2022) 32–46
hydroxy-3-methyl-glutaryl-coenzyme A) reductase pathway from
acetyl-coenzyme A (Monje-Galvan and Klauda, 2017). Algae based ste­
rols also show potential biological activity to mark them as suitable
candidate against anti-inflammatory reactions and others (Hannan
et al., 2020). It has been observed that sterols such as fucosterol,
ergosterol and chondrillasterol are widely obtained from Phaeophyceae
whereas cholesterol was obtained in more amounts from Rhodophyceae
(Yadav et al., 2021).
2.1.3. Vitamins
Vitamins either water-soluble or fat-soluble are an important class of
micronutrients required for the better metabolism and physiology of the
human body. Despite the fact that vitamins are crucial entities of human
life, their production is insignificant. This paves the way for wide
investigation on photo synthetically active and rapidly dividing algal
species since the vitamin accumulation is reported to be higher in them
(Ehsan et al., 2021). Elevated amounts of vitamins such as Vitamin B2,
B3, B9, B12 along with Vitamin E and C have been reported in green
algal strain, Dunaliella salina (Çelebi et al., 2021). Likewise, high con­
centration of Vitamin C was obtained from marine diatom species,
Skeletonema marinoi and Chaetoceros sp. High concentration of Vitamin A
was also reported from Chaetoceros sp. (Bhattacharya and Price, 2020).
Vitamin E was reported in the algal species, Haematococcus pluvialis
(Shehata et al., 2020). Diatom, Skeletonema marinoi and marine green
alga, Tetraselmis suecica were reported to accumulate high Vitamin E in
their body mass (Milito et al., 2020). Similarly, another diatom, Skel­
etonemaco statum was investigated for the presence of vitamins. It was
reported to accumulate Vitamin K1 in high content (Carballo-Cárdenas
et al., 2003). Thus, algal extracts are rich in vitamin supplements too
which are necessary for maintaining stimulation of various
A. Ahirwar et al.
physiological body functions.
2.1.4. Proteins (Lectins)
Proteins form the backbone of a living organism. Almost every
function, morphological structure in a living organism requires protein
in one or the other form. Breakdown of proteins gives rise to peptide
chains which are biologically active against various human ailments
such as cancer, inflammatory diseases and neurodegenerative diseases
(Admassu et al., 2018). Protein degradation from Chlorella vulgaris, a
green microalga produces biologically active peptides that have anti­
cancerous activity (Zhang et al., 2017). The composition of both
microalgae and macroalgae shows the inclusion of all the essential
amino acids which aren’t synthesized by the normal human body
(Mišurcová et al., 2014). Thus, these essential amino acids help in pre­
venting the cells from damage and attack of free radicals and other in­
flammatory agents. Palmaria palmata, a member of the Rhodophyceae
class of algae comprises of essential amino acids such as leucine, valine,
methionine along with isoleucine and threonine which resembles the
protein content present in egg white protein, ovalbumin and legume
protein content respectively (Bjarnadóttir et al., 2018).
Talking of another diversified class of peptides synthesized from
algae are the lectins. They contain distinct and specific domains for
carbohydrate binding. The high specificity of lectins towards the car­
bohydrate moieties is what makes it so vital in the development of new
drugs that are able to target the bacterial, viral and fungal species
(Ogawa et al., 2011). Some of the most widely investigated lectins are
griffithsin, extracted from red alga, Griffithsia sp. (Besednova et al.,
2021). Lectins are basically carbohydrate-binding proteins derived from
plants as well as from algae and are mostly considered as antiviral drugs.
They protect us from the first line of pathogens mainly bacteria and
viruses due to its specificity and reversibly. It was found that lectins have
more than two binding sites which connects to the pathogen and do not
let it spread throughout the body. Currently new lectins have been
derived from red algae that are not homologues to other protein family
but have very high conserved sequence. They are Cyanobacterium,
Oscillatoria agardhii (OAA), Eucheuma serra and Kappaphycus alvaresii
(KAA-2). These algae derived lectins are found to be very special
because of their unique and specific binding with carbohydrates for high
mannose (HM) glucans. These lectins at nanomolar concentration are
very active as antivirals agent, for examples for influenza virus due to
presence of high mannose glycans (Besednova et al., 2019). Carbohy­
drate form of lectins derived from red algae are also very effective in
fighting the viruses and has potential for prognosis and selective treat­
ment of these diseases (Righini et al., 2019).
Several investigations are being carried out for the development of
algae based antimicrobial peptides for battling the rise in microbial
diseases. The types of amino acid modification have also received quite
some attention. Specific peptides extracted from Tetraselmiss uecica were
subjected to single amino acid alteration, hence mutating lysine to
alanine which eventually led to better antibacterial activity against su­
perbug methicillin resistant Staphylococcus (Guzmán et al., 2019).
Similarly, the essential amino acids namely, leucine, phenylalanine and
valine are the major constituents of Ulva rigida, a green alga (Paiva et al.,
2017). With proper research and development, algae-based protein
metabolites could become key players in the global war against micro­
bial resistance. Hence concluded that lectins are considered as most
promising algae for antiviral activity in a search to find a drug against
Sars-COV-2 strain for COVID-19.
2.2. Macroalgae
2.2.1. Protein (Griffithsin)
Griffithsin (GRFT) is an isolated lectin derived or extracted from
macroalgae Griffithsia sp.,(red seaweed) which is extensively studied as
the anti-HIV-1 protein(Barre et al., 2019). Due to its homology to other
known proteins and high capacity to restrict HIV-1 they help in forming
37
Journal of Biotechnology 349 (2022) 32–46
antibody, inhibit cell fusion and cell to cell transmission (Barre et al.,
2019). It is now considered as most potent protein for inhibiting HIV
virus till date (Lo et al., 2020). It is also studied against many viruses and
show potential activities as antiviral agents (Cirne-Santos et al., 2019b),
Hantaviruses(Yusof and Rothan, 2020) and corona viruses, MERS-CoV
and Corona virus. HIV-1 contains majority of N-linked glycans which
overwhelmingly bind with the terminal mannose of lectins (Man5­
–95GlcNAc2 structure) associated with Arganine (N). GRFT blocks the
binding sites of gp120 corresponding to cell receptors and isolates HIV-1
and HIV-2. GRFT is also known for its safety on various cell lines
including the cervical canal cells (End1/E6E7, Ect1/E6E7, CaSki), fi­
broblasts (3E3) and dendritic (moDc) cell lines (Besednova et al., 2019).
GRFT is considered also mainly because of its undesirable side effects
and minimum chronic toxicity and proven no irritation on vaginal part
in the rabbit model.
Griffithsin has also been considered for the treatment of corona virus
(Iravani and Varma, 2021). Since a 2019, pandemic calling for repur­
posing old drugs and coming out with more prophylactics and treatment
rather than opting new discoveries. For example, Remdesivir was pre­
viously used for the treatment of Ebola virus but now it is being
considered for treatment of corona virus infections too and had passed
clinical trials phases I and II in vivo and in vitro. It is now verified and
used directly on patients at earlier stage of infection. Therefore GRFT
can also be considered to repurpose its applications for the treatment of
Corona virus patients due to its potential prophylactic activity for
humans and animals proven by clinical trials as antiviral for HIV
(Siqueira et al., 2017a).
It is concluded that GRFT binds with the glycosylation sites in the S1
subunit, possibly the receptor binding domain (RBD), of Corona virus S
protein sites and therefore proven to be inhibiting pseudo typed and live
Corona virus. Also, when combined with pan-CoV fusion, it helped in
inhibiting the viral infection and exhibit synergistic effect against
Corona virus. It is already known that GRFT can be produced in the bulk
amount and can be used as antiviral agent for many viruses and now for
corona virus too, which can be used in combination with EK1 as nasal
spray or inhalation formulation for the treatment of corona virus.
Therefore GRFT must be considered as God Gift for humankind as it help
us in preventing and fighting against many viruses Its gel form can be
very promising and useful antiviral product that may prevent sexual
transmission of Corona virus(Siqueira et al., 2017a).
2.2.2. Carrageenans
Carrageenans are the red algae derived polysulphate groups having
disaccharide repeating unit, of α-1,3-glycosidic bond and β-1,4-glyco­
sidic bond consisting mainly of D-galactose residues (Frediansyah,
2021). It is structurally diverse because of β-1,4- linkage and presence of
3,6-anhydrogalactose, and number of sulphated groups present in the
monosaccharide unit which help in contributing antiviral activity.
Among all the polysaccharides, carrageenans are most studied sulphated
polysaccharide for toxicity, pyrogenicity, allergenicity and are verified
and confirmed by various studies to be used in foods and medicines. It
has been observed that enveloped or unenveloped internal part of virus
from host cell which may include virus strain like HsV, HIV(Pagarete
et al., 2021), Hepatitis-A, Human papilloma viruses(Kwon et al., 2020),
Dengue virus(Pérez et al., 2016), Rhinoviruses (Golke et al., 2021),
Japanese encephalitis virus (Davis et al., 2021), Murine cytomegalovirus
(Piersma et al., 2020) and Tobacco mosaic virus(Venturuzzi et al., 2021)
are selectively inhibited by Carrageenans.
Recently, carrageenans are also found effective for inhibiting Japa­
nese encephalitis virus (Li-Beisson et al.) replication which is a family
virus of Flaviviridae leading human disorder, due to which it is
considered as an endemic disease. It was found that Carrageenans were
able to inhibit the JEV at half maximal effective concentration (EC50) of
15 μg/mL with cytotoxic concentration (CC50) greater than 200 μg/mL
compared to that in human liver cells (WRL68). Thus carrageenans are
able to show substantial antiviral activity because it starts inhibiting the
A. Ahirwar et al.
viral entry at initial stage thus confirming it as potential antiviral agent
(Fischer et al., 2020) another way of trial against SARS-COV-2 strain.
2.2.3. Fucoidans
Fucoidans are the diverse class of polysulphated heterogeneous
structure consisting of L-fucose and sulphate residue groups (Lee, 2019).
It is extracted from the cell walls of brown seaweeds or macroalgae
having monosaccharide residues. Fucoidans show various therapeutic
activities (Jain et al., 2020). This is probably due to the fact that they are
less harmful and non-toxic thus making them facile molecule to treat
many diseases. Interestingly fucoidans have potential to show antiviral
activities for corona virus, HIV, HsV, Influenza virus, human cytomeg­
alovirus, bovine viral diarrhea virus and murine norovirus (Vimala
et al., 2021). These molecules have ability to inactive the virus infection
even by coming in direct contact (Pagarete et al., 2021). The physiology
of action of fucoidans involves their sulphate group blocking the entry of
virus into the host by competing for the attachment of positively charged
virus glycoprotein envelope onto the host cell. Recently sulphated
polysaccharide (fucoidan) isolated from the brown seaweed Saccharina
japonica acted as an inhibitor for Sars-COV-2 against COVID-19 to
multiply and give strong competition to Remdesivir drug, which is
currently being used for the treatment of severe COVID-19 patients
(Kwon et al., 2020).
2.2.4. Ulvans
Ulvans are extracts from green algae seaweed especially from genus
Ulva which are edible due to its enrichment with potentially high
bioactive components. The sulphur polysaccharide (SPS) from Ulva is
rich in fibers, help in reducing chronic diseases as well as help in pro­
moting the gastrointestinal health thus act as immunomodulating,
antiviral, antioxidant, antihyperlipidemic and anticancerous high value
compounds (Kidgell et al., 2019). The antiviral activity of ulvan has also
been seen in the enveloped viruses of herpes simplex virus (HSV) (Lopes
et al., 2017), Newcastle disease virus (NDV), Japanese encephalitis virus
(Li-Beisson et al.), dengue virus (DENV), yellow fever virus (YFV), West
Nile virus (WNV), influenza (H1N1), avian influenza virus (Paiva et al.)
and measles virus (MeV) (Pereira, 2018). It also showed antiviral ac­
tivity in vitro performed in the human larynx epithelial carcinoma cells
(Hep-2) (Jabeen et al., 2021). Also 100% inhibition is shown by highly
sulphated ulvan (SO32- = 22%) from U. compressa (Tang et al., 2021). In
vitro, using vero cells, ulvan can inhibit virus to enter in the cell at half
maximum inhibitory concentration (IC50) range of 0.1 μg/mL.
2.2.5. Diterpenes
Diterpenes are heterogeneous natural products derived from brown
algae having sufficient efficiency as antiviral drug agents due to their
pharmacological functionality. As the name indicates they have two
terpenes unit connected together. Several diterpenes were studied and
found effective in action against viruses, specially HIV (vonRanke et al.,
2020). These were mainly from order Dictyotales having brown algae
particularly genus Dictyota. It was found that Dictyota menstrualis extract
showed satisfactory results in stopping replication of Zika virus up to
74% (Cirne-Santos et al., 2019a).
2.3. Cyanobacteria
2.3.1. Spirulan
Spirulan extracted from Arthrospira platensis (popularly known as
Spirulina) is SPS (Freitas et al., 2021) used for showing antiviral activity
against mumps virus, measles virus, HiV-1, HsV-1, human cytomegalo­
virus and influenza A virus (Zhao et al., 2020). Specialty of this SPS is
that it is more effective than dextran sulphate and can help directly to
inhibit the penetration power of virus. It exists in ionic form with cal­
cium or sodium, however, calcium spirulan is not been able to fight
effectively with enveloped viruses like Poliovirus and Coxsackie virus
(Yasuhara-Bell and Lu, 2010). On the other hand, it showed great
38
Journal of Biotechnology 349 (2022) 32–46
inhibition effect in vitro for HsV-1, HsV-6, human cytomegalovirus and
HIV-1(Pagarete et al., 2021; Petit et al., 2021). Calcium spirulan is
among the best SPS used to block the anchorage and entry of the HsV-1
virus into mammalian epithelial cell more as compared to acyclovir
(Petit et al., 2021) and also block the entry of Kaposi sarcoma–associated
Herpes virus/HsV-8 (Pagarete et al., 2021). Hence, spirulan serve as a
potential therapeutic agent for antiviral activity. Photosynthetic cya­
nobacteria as well as red algae comprise of phycobilins (phycoery­
throbilin, phycourobilin, phycocyanobilin and phycourobilin) which are
linear tetrapyrrole chromophore compounds, covalently linked to phy­
cobiliproteins. Pendyala et. al. 2021 (Pendyala et al., 2021) reported via
molecular docking that phycocyanobilin has the potential therapeutic
and antiviral activity against SARS-CoV-2 (Mader et al., 2016; Pendyala
et al., 2021). Moreover, these phycobiliproteins are fluorescent having
their significant role in detection and inhibition of multiplication of
cancer cells (Ismail et al., 2021; Singh et al., 2017b).
2.3.2. Cyanovirin-N
Cyanovirin-N, extracted from cyanobacteria, Nostoc ellipsosporum
consisting of polypeptide chain of more than 100 amino acids formed
due to the presence of cysteine residues in a quadruplet form (de
Siqueira Castro et al., 2021). Cyanovirin-N, a most studied algal lectin
having 11 kDa-amino acid (AA) long polypeptide chain, has four
cysteine residues that form two intra-chain di-sulfide bonds and are
derived from cyanobacteria Nostoc ellipsosporum (Carpine and Sieber,
2021). Its antiviral activity is due to its fundamental protein structure
which binds with HIV’s envelope protein gp120 and restrict its binding
with the chemokine CCR5 and CXCR4 co-receptors and host CD4 T-cell
receptor (Wang et al., 2021). Its action has been studied mostly for HIV
virus but its potential antiviral activity in inhibiting other viruses en­
velops such as Herpes simplex virus, Influenza virus, Measles virus and
Ebola virus is also observed (Carpine and Sieber, 2021). Among various
antivirals targeting specific oligosaccharides, CV-N is a promising
candidate for preventing sexually transmitted diseases too. When its gel
form was treated with Macasa fascicurlaris, a female macaques, it in­
hibits chimera of HIV viruses (Janahi et al., 2018). HIV transmission can
thus be restricted to up to 63% when macaques with a Lactobacillus
were dosed vaginally. Notably side effects of CV-N were tested in vitro
treatment with peripheral blood which showed mitogenicity, cell acti­
vation and increased cytokine production. Other way to enhance the
CV-N antiviral activity is to blend it with more plant derived antibody
mAb b12 that helps in neutralizing HIV infection(Pagarete et al., 2021).
Extended CV-N with Gly4Ser linker also showed effective inhibiting
activity for HIV viruses.
2.3.3. Scytovirin
Scytovirin (SVN) yet another bio compound extracted from cyano­
bacterium Scytonema varium exhibits anti-HIV activity consisting of 95
amino acids long chain, which helps in inhibiting HIV replication in
vitro. But its antiviral activity is somehow lesser than GRFT and CV-N
because of significantly higher IC50 values (Alexandre et al., 2011;
Janahi et al., 2018). Therefore, it has strong binding affinity with
mannose rich oligosaccharides with the glycoprotein rich envelope of
other viruses. And thereby it is having blocking potential for the target
and help in spreading lesser infection. Hepatitis C virus replication in­
hibition by SVN is the good example out there, showing its potential for
blocking targeted cells (Garrison et al., 2014). On the offset, Zaire Ebola
viral infection is rarely inhibited by SVN because of its highly patho­
genic nature (Ercolano et al., 2019). Little inhibition of Ebola virus in
vitro can be seen at EC50 concentration of 50 nM which is lesser than
CV-N. Also at same concentration, it has been seen that it also helps in
preventing the replication of the Agola strain related to Marbug virus
(MARV). Molecular dynamics calculations predicted this SVN, when
interacted with single-stranded RNA Dengue virus, as one of the best
protein candidate used against fighting with destructive Flavivirus,
which is responsible for circa 400 million human infections per annum
A. Ahirwar et al.
(Ercolano et al., 2019). SVN is produced in ng/L concentration from
native cyanobacterium, Scytonema varium. Therefore for efficient and
frequent use of SVN as microbicide, its production efficiency should be
enhanced when expressing it with Escherichia coli producing 10 mg/L of
SVN thus showing anti-HIV activity(Pagarete et al., 2021). Currently
anti- HIV activity also found when SVN expresses with intravaginal
isolate of Lactobacillus plantarum(Vimala and Poonghuzhali, 2017).
2.3.4. Microvirin
Microvirin (MVN), extracted from cyanobacteria, Microcystis aero­
ginosa consists of a long polypeptide chain of 108 amino acids with α-1,2
mannose sugar moiety recognizing glycan terminal (Takaara et al.,
2019). Microvirin is one such newly isolated algal protein derived from
Microcystis aeruginosa cyanobacteria having single glycan binding site
with 108 amino acid sequence. It exists in monomeric form in solution
and allow to bind with terminal α-1,2- mannose sugars. It neutralizes in
nanomolar concentration against broad range of HIV-1 strains. Whereas
it has simpler similar structure like CV-N but possess less toxicity and
mitogenicity than CV-N and therefore it is considered more potential
microbicide than CV-N because of single glycan binding site and foot­
print of gp120 glycan binding. It has also been found that its efficiency
against HIV-1 is more than CV-N because it showed the creation of a
bifunctional chimera with dual action virus and its entry restrictions. On
Fig. 3. Antiviral activity of algae metabolites against different virus functions.
39
Journal of Biotechnology 349 (2022) 32–46
the other hand, Hepatitis C virus inhibition can also be done by the help
of potentially active antiviral oligomeric engineered microvirin
(Pagarete et al., 2021; Sit et al., 2018).
3. Action against pathogens
Lectins are proteins obtained from certain types of cyanobacteria
have significant antiviral properties (Carpine and Sieber, 2021). Also
fatty acids from algae have been known for effective antibacterial ac­
tivities (Hossain et al., 2021). Henceforth the various value-added me­
tabolites from algae are reservoir for healthy life. These value-added
products from red, green, golden and brown algae alone or in combi­
nation with other metabolites and chemicals have capacity to show re­
lief against various ailments in medical science. These metabolites are
treasures drugs from the depth of oceans which show inhibitory action
against replication of viral and other pathogenic DNA and RNA as
elaborately shown in Fig. 3. This obviously makes pharmacological
market have a broad spectrum of bioengineered compounds from algae
of interest (Besednova et al., 2021; Keshri, 2012). Furthermore these
derived drug from are effective in treatment with negligible side effects
(Deniz et al., 2017; Sandhya and Vijayan, 2019). The role of some
specific algae against different pathogens and their bio compounds used
for their treatments are discussed in the following subsections.
A. Ahirwar et al.
3.1. Algae metabolites as antivirals
Viruses infect both humans as well as animals and have huge
biodiversity on the earth. Although 99.99% viruses are not so threat­
ening but some of them are dreadful. For example, viruses such as the
hepatitis C, human immunodeficiency virus, herpes, dengue virus, Ebola
virus (Wang et al., 2019) and the most recent corona virus (Jain et al.,
2020), all are affecting humans worldwide in large scale. There is still no
proper and permanent immunotherapy treatment and vaccination to
cure the diseases spreading due to virus. Viruses are believed to effect
and damage almost any vital organs of human body. Therefore, proper
treatment and medication for such infectious diseases is needed. Hence,
it is not surprising to consider algae as the most vital potential ingredient
for the bio-medications of antiviral drugs(Gupta et al., 2021). Till the
starting of 21st century there were only ten licensed antiviral drugs but
this number has been seen increasing day by day as researchers are
putting their efforts to understand the virus physiology. Naturally
occurring products from algae such as carrageenan, cyanovirin or grif­
fithsin are potential bio compounds from algal extracts to be used as
antiviral agents(Pagarete et al., 2021). However, it needs more consis­
tent research efforts to discover such natural products as antivirals
agents.
Seaweeds extracts such as Osmundaria obtusiloba used as antiviral
agent against ZIKA virus and opens many challenges for researchers to
identify the main factors affecting this treatment because vaccine and
treatment facilities for this virus is still under testing. But the extract
from O. obtusiloba algae provides an effective relief for the patients
infected from this virus. Results like this encouraged scientist for more
such findings against ZIKA virus or to develop more such antiviral drugs
(Fischer et al., 2020). Brief study on different antiviral natural products
is discussed below.
3.2. Algae metabolites as antibacterials
Marine algae have a natural matrices that have been explored for
their uses in pharmaceutical industries because of bioactive metabolites
(Lopes et al., 2017). Different marine algae such as Rhodophyceae (red),
Chlorophyceae (green), Phaeophyceae (brown), Chrysophyceae (Shtaida
et al., 2014) and Bacillariophyceae (diatom) are all screened to identify
their antibacterial activity (Jain et al., 2020; Piwowar and Harasym,
2020; Shannon and Abu-Ghannam, 2016; Song et al., 2020). It has been
studied and suggested that terpenes, polypeptides, quinones and alka­
loids from marine algae showed potential antibacterial property which
could be further used as drug delivery agents (Kini et al., 2020). On the
offset, it has been observed that marine extracted natural products such
as polysaccharides, tannins, flavonoids, phenolic acids, bromophenol,
and carotenoids, shows different biological behavior in different sol­
vents. Therefore, for obtaining finest results, the antibacterial properties
of bio compounds from algae utmost care should be taken regarding
choice of solvent system. Individual pathogens and inhibition of their
amplifying whole cell as well as genetic material by biocompounds and
value-added products form algae are henceforth detailed in a compre­
hensive manner.
3.2.1. Escherichia coli
Escherichia coli is a rod-shaped bacterium which grows at tempera­
ture of around 37 ◦ C responsible for significant diarrheal and extra in­
testinal diseases. European Union reported that, a total of 2.28 citizens
per 100,000 habitants were affected with food poisoning by E. coli in
year 2018 (Silva et al., 2020). Therefore, there is an urgent need of
antibacterial drugs or antibacterial natural compounds to give compe­
tition to the bacteria without any delay. However, various studies on
marine algae are done to improve the efficacy of algal based drugs
against antibacterial diseases (Raja et al., 2013).
It has been seen that marine seaweeds Ulva prolifera, Gracilaria
lemaneiformis, and Sargassum fusiforme showed strongest antibacterial
40
Journal of Biotechnology 349 (2022) 32–46
effect in ethanolic extract (Li et al., 2018; Zerrifi et al., 2018). Further­
more green macroalgae extract of Halimeda sp. showed better antibac­
terial activity at different concentrations against Bacillus subtilis,
Staphylococcus aureus and Bacillus cereus, yeast and mold (Susilowati
et al., 2015). Besides this in vitro results have revealed that brown algae
Hydroclathrus clathratus, showed maximum antimicrobial property
against bacteria and fungi (Vimala and Poonghuzhali, 2017).
Amongst differently colored algae, it has been observed that brown
algae strongly inhibits the bacterial growth and show the inhibition zone
up to 18 mm of diameter, which is either susceptible or intermediate
(ANTI et al., 2021). When an acetone-based crude extract of Cutleria
multifida is subjected for testing E. coli bacteria, it was found that the
minimum inhibition concentration ranged from 7.5 mg/L to 0.16 mg/L
(Silva et al., 2020). Gracilaria multipartite, Corallina offciinalis, G. corti­
cata and Rhodomela confervoides, showed high range of antibacterial
property against E. coli. On the other hand bioactive pigments such as
carbohydrates, phenolics, flavonoids, fatty acids, tannin, proteins,
chlorophyll, carotenoids, phycoerythrin and phycocyanin from red
macroalgae Laurencia papillosa showed less minimum inhibitory con­
centration (MIC) value of 0.2 mg/mL(Silva et al., 2020).
3.2.2. Enterobacter sp
Enterobacter sp. is pathogen with about 12 species commonly found
in food products. However, amongst 12 such species E. cloacae and
E. aerogenes are mainly responsible for human infections (Stokes et al.,
2021). To overcome this effect biocompounds from marine algae were
tested against the bacteria. It was found that brown algae belonging to
phylum Phaeophytha was found resistant or showed no antimicrobial
activity (Silva et al., 2020). However, Ulvan from U. reticulata showed
great antibacterial property against Enterobacter sp. The satisfactory
results were obtained as inhibition zone reached about 20 mm of
diameter in inhibition growth zone experiment (Tziveleka et al., 2019).
Thus U. reticulata is the only green algae extract which provide best
results as antibacterial agent for this bacterium.
3.2.3. Salmonella sp
Salmonella sp. bacteria is the major cause of salmonellosis disease
which is the major health hazard worldwide (Popa and Papa, 2021).
This bacterium is usually found in food like beef, chicken, eggs, fruit,
pork, sprouts, vegetables, some of the frozen foods like nut butter, frozen
pot pies, chicken nuggets and stuffed chicken entries, which makes
human’s fall sick and acquire this disease. This food borne bacteria not
only affecting humans but also show their worse effect on animals, and is
able to spread from person to person. Infection spread by non-typhoidal
Salmonella in frozen pies around the world was reported in the year 2019
(Ehuwa et al., 2021). Another study in Asia showed 159 meat samples
out of 807 were found positive for Salmonella (Yang et al., 2019).
Prevalence of Salmonella was highest about 16% in beef compared to
10.9% in mutton, 6.6% in dumplings and 3.6% in smoked pork (Yang
et al., 2019). In the year 2018–2019, 255 cases for Salmonella by beef
and soft cheese were reported for multidrug resistance against Salmo­
nella in the United States (Soria-Herrera et al., 2021). In yet another
work it was revealed that 384 chicken caeca collected and studied
showed 14.6% infection by Salmonella thus showing its universality. So,
to fight against this bacteria, marine algal extracts were chosen and
widely explored. Most of the antimicrobial studies with algal extract
were done on the Salmonella typhi out of all the Salmonella species. The
studies showed inhibition growth zone of diameter greater than 15 mm
when algal extracts were from Phaeophyta phylum viz; Dioscorea
membranacea, Padina gymnospora, Dictyota dichotoma var intricate, Dic­
tyota indica (Silva et al., 2020), Scytosiphon lomentaria and Ecklonia cava.
U. rigida and Calendula officinalis. Additionally extracts from Chlor­
ophytes and Rhodophytes also showed inhibition effect against S. typhi.
Therefore, it is said that, marine algal compounds are potentially
very active compounds to inhibit the bacterial growth and hence
represent the future aspects of common antibiotics. This increases the
A. Ahirwar et al. Journal of Biotechnology 349 (2022) 32–46

crisis of resistance of pathogens, algae are thus the "Sunlight in the dark" Table 2
i. e. hope for new and effective antibiotics which should be explored and Marine algae extracts their sources and properties.
developed as possible antimicrobial agents against COVID-19 pandemic. Extracts Source Properties References

Astaxanthin Haematococcus Antioxidant, (Yu et al.,

3.3. Algae metabolites as antifungals pluvialis antiinflammation 2021)
Griffithsin Red Macro Algae Antiviral (Lee, 2019)
One of the threat to human health observed worldwide is due to (Griffithsia sp.) Antibacterial (SonAwAne
and Arya,
fungal infection, in which morbidity and mortality are reported in most
2018)
of the cases(El-Hossary et al., 2017). Moreover, there were very few Antioxidants (Decker et al.,
antifungal drugs present in the market and therefore it increases the 2020)
demand for more antifungal drugs. Synthetic drugs have side effects and Spirulan Blue-green Micro Antiviral (Mader et al.,
take time to be developed and get into the market, whereas drugs pre­ Algae Antioxidant 2016)
(Spirulina Antibody
pared by green synthesis with lower side effects are more sought-after
platensis) Anti-inflammatory
and marketable(Besednova et al., 2020). Algal drugs are gaining Anti-allergic
importance in this aspect especially in treatment of fungal diseases. Anticancer
Moreover, algae are considered to be the first choice for antimicrobial Mycroviran Blue-green Macro Antiviral (Parajuli et al.,
Algae Antioxidant 2018).
drugs due to the exceptional structural diversity exhibited by their
(Microcystis
biologically active secondary bio metabolites which can act against aeruginosa)
many microbes such as bacteria, fungi and even viruses (Ercolano et al., Ulvans Green Macro Antiviral (Hans et al.,
2019). Algae 2020)
Therefore, scientists are working on customizing the algal derived Antioxidant (Yaich et al.,
2017)
drugs which will be beneficial for society to fight against fungicidal
(Ulva, Gayralia, Antifungal (Yaich et al.,
diseases. Infection in skin, hair and nails due to fungus are referred to as and Monostroma) 2017)
dermatophyte and the drugs which cured the diseases caused by such Antibacterial (Cindana et al.,
infection are anti-dermatophyte. In 2018, 48 extracts from medicinal Anti-inflammatory 2020; Reis
plants and marine algae were studied at different solvent extracts. Me­ Anticancer et al., 2018)
Diterpenes Brown Macro Antiviral (Chen et al.,
dicinal plants such as Cibotium barometz, Melastoma malabathricum, Algae Cytotoxic 2018)
Meuhlenbeckia platyclada, Rhapis excelsa, Syzygium myrtifolium, Vernonia (Dictyota, D. Antioxidant
amygdalina and marine macroalgae extract from Caulerpa sertularioides, dichotoma var. Antifouling
Kappaphycus alvarezii were tested in vitro in different solvents such as implexa) Antitumor
Laminarans Brown Macro Anti-tumor (Sanjeewa
hexane, chloroform, ethyl acetate, ethanol, methanol and water. They
Algae et al., 2017)
were studied against Trichophyton rubrum and Trichophyton interdigitale (Undaria Anti-Apoptotic
fungal strains (ATCC reference strains) on African monkey’s kidney pinnatifida,
epithelial (Vero) cells (Sit et al., 2018). The experiment was performed Saccharina
for antidermatophytic activity based on the colorimetric broth micro longicruris)
Porphyran Red Macro Algae Antioxidant (Zhang et al.,
dilution method and kept the viability of Vero cells at Neutral Red up­ 2010)
take assay for measurement (Sit et al., 2018). Remarkable results were Antiallergic (Vo et al.,
obtained i. e. all the extracts from medicinal plants and from marine (Porphyra) Anticancer 2015)
algae show antifungal effect except the water extracts of V. amygdalina, Antitumour
Antiviral
C. sertularioides and K. alvarezii against Trichophyton sp. Various algae
Antifatigue
extracts and their potential to treat various pathogenic ailments is Antibacterial
shown in Table 2. Anticoagulant
Worth to mention here that; one of the major health problems in Rhamnans Green Macro Antiviral (Terasawa
metro cities is Asthma for humans of all ages with characterized symp­ Algae Antibacterial et al., 2020;
Tsubaki et al.,
toms and airborne fungus increases its mortality. Extracts from marine 2016)
algae Acanthaophora specifera, Cladophoropsis sp., Laurencia paniculata, (Monostroma Antifungal (Wu, 2017)
Tydemania sp., and Ulva prolifera were extracted and tested against the latissimum) Anti-inflammatory
selected bronchial asthmatic fungus. Samples of 45 patients were Antioxidation
Antitumor
collected and 15 sputums were isolated for the antifungal activity test.
Antioxidant
Maximum amount of antifungal activity was shown by L. paniculate Galactans Red Macro Algae Antiviral (Kora and
followed by U. prolifera, Cladophoropsis sp., A. specifera, and Tydemania Anticoagulant Rastogi, 2018)
sp. in ethanolic extract (Mickymaray and Alturaiki, 2018). Therefore Antioxidant
L. paniculata is proven to be the most eligible macroalgae for repre­ (Anogeissus Antifouling
latifolia.) Antitumor
senting antifungal effect. Minimum fungicidal concentration (MFC) and Antiadhesive
MIC of ethanolic fraction was about 125–1000 µg/mL and Antithrombotic
125–500 µg/mL respectively for the algal extracts. This report suggested Anticancer
that marine algae are the excellent source of bioactive metabolites Antibacterial
Exopolysaccharide- Green Micro Algae Antiviral (Liu et al.,
which are useful for giving huge competition to fight fungal pathogens
des (EPS) (Chlorella sp., Anti-inflammatory 2016)
and help in stopping the fungal growth, replication and provide cure and Phaeodactylum Antitumor
relief in asthmatic diseases (Mickymaray and Alturaiki, 2018). tricornutum)
Galactofucans Brown Macro Anticancer (Zhang et al.,
4. Knowledge gaps and future perspectives Algae 2021)
(Undaria Anti-aging (Chen et al.,
pinnatifida, 2021)
With the outbreak of SARS-CoV-2, there has been a huge trial of Anti-inflammatory
drugs at every level, be it allopathic, homeopathic or ayurvedic drugs (continued on next page)
(Ali and Alharbi, 2020). However, all the chemical compounds

41
A. Ahirwar et al.
Table 2 (continued )
Extracts Source Properties References
Saccharina Antibacterial (Beaulieu
longicruris) Anticoagulant et al., 2015)
Anti-tumor
Anti-Apoptotic
Anti-Thrombosis
(Xylo)mannans Red Macro Algae Antiviral (Jin et al.,
2020)
(Scinaia hatei, Anticoagulant (Son et al.,
Sebdenia Anticancer 2013)
polydactyla) Antibiotic
ultimately are synthesized from plants or animals. Despite of the fact,
algal extracted drugs have high potency against many pathogens
(Magda et al., 2021). But again, marine extracts in form of drugs are still
in its infancy. And awareness of its properties and functioning is still
required so that it should get more fame and get explored more for its
various exclusive applications. It is economical and health effective with
no side effects and which should get more spot light for human welfare.
Production of algae derived drugs are no doubt energy saver. However,
there are very few algal drugs available in the market, therefore
knowledge gaps should be strengthened among masses and scientific
community to know the strength and potential of algal polysaccharides
against deadly viruses including Corona virus. The sulphated poly­
saccharides have strong antiviral properties and marine algae are rich
source of these polysaccharides (Lee and Ho, 2021). However, many
algae have thick cell walls and need pretreatment for the extraction of
algal metabolites (Ahirwar et al., 2021a; Khan et al., 2021). Amongst the
pretreatment methods also there is urgent need to select which method
is economical since either of the present methods viz; solvent method,
high pressure, microwave, ultrasound require high operational costs.
The current understanding of the effect of algal metabolites and their
antimicrobial activity is based almost completely on data from in vitro
and in vivo animal studies. Though, these data could not be induced to
the human environment, and further reliable human clinical studies are
needed to determine the actual effectiveness of algal polysaccharides
and other metabolites in the viral, bacterial and fungal inhibition and
treatment will fill the knowledge gaps between pharmaceutical appli­
cations and the scientific background of those applications (Ouyang
et al., 2021). Further, more research needs to be done on testing antiviral
properties from marine flora especially micro and macroalgae. On the
contrary, the curiosity to unravel the hidden treasures of ocean however
has taken a slow start compared to mankind’s curiosity for challenging
mission at Mars.
5. Conclusions
With continuous investigation and development of marine resources,
the efficient bioactivity of algae and their metabolites are playing a
progressively significant role as functional food and nutrition for human
health. Numerous algal metabolite derived drugs are now being tested in
clinical and experimental settings. Macro and microalgae are rich in
carotenoids, sulphur polysaccharides, lipids, proteins and vitamins
which are not only required for healthy life but also have the potential
effectiveness in prevention and treatment of various infectious and life
threatening viruses such as SARS-CoV-2. Although very limited studies
are done on testing antiviral properties of algal metabolites against the
outbreak of numerous diseases. The risk of infectious diseases can
eventually be reduced if nutritious diet can be upgraded with some
compulsory algal derived food and supplements. Hence, this review
offers a bird’s eye view on the obtaining and utilizing naturally occur­
ring marine and fresh water algal resources for treatment of many ac­
quired and inherited diseases. Overall, this review concludes algae as a
huge reservoir and treasure for high value-added biocompounds and
their tremendous applications in food, nutraceuticals, pharmaceutical,
42
Journal of Biotechnology 349 (2022) 32–46
cosmetics and other industrial sectors.
Code availability
All data, models, and code generated or used during the study appear
in the submitted article.
Ethics approval
Not applicable.
Consent to participate and consent for publication
The submitted paper here has not been published previously and is
not under consideration for publication elsewhere, its publication is
approved by all authors. If accepted, it will not be published elsewhere
in the same form, in English or in any other language, without the
written consent of the Publisher.
CRediT authorship contribution statement
Ankesh Ahirwar: Literature review, Writing – original draft, Data
curation. Khushboo Kesharwani: Literature review, Writing – original
draft, Data curation. Rahul Deka: Literature review, Writing – original
draft, Data curation. Shreya Muthukumar: Literature review, Writing –
original draft, Data curation. Mohd. Jahir Khan: Writing – review &
editing. Anshuman Rai: Writing – review & editing. Vandana
Vinayak: Conceptualization, Supervision, Writing – original draft,
Writing – review & editing, Funding acquisition. Sunita Varjani:
Conceptualization, Supervision, Writing – original draft, Writing – re­
view & editing, Resources. Khashti Ballabh Joshi: Writing – review &
editing. Shruti Morjaria: Writing – review & editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Data Availability
All data, models, and code generated or used during the study appear
in the submitted article.
Acknowledgements
MJK is thankful to Department of Science and Technology Nano­
mission Government of India for the Post doc fellowship. AA is thankful
to CEFIPRA Indo French project for Pre doctoral fellowships. VV would
like to thank Department of Science and Technology Nanomission
Government of India research project number (SR/NM/NT-1090/2014
(G) and Indo-French Centre for the Promotion of Advanced Research
(IFCPAR/CEFIPRA) project number (PPMB-7133/2020) Indo France
Project sanctioned to VV for the financial aids.
References
Abu, F., Jabar, J., Yunus, A.R., 2015. Modified of UTAUT theory in adoption of
technology for Malaysia small medium enterprises (SMEs) in food industry. Aust. J.
Basic Appl. Sci. 9, 104–109.
Aditya, T., Bitu, G., Mercy Eleanor, G., 2016. The role of algae in pharmaceutical
development. Spec. Issue Rev. Pharm. Nanotechnol. Res. Rev. J. Pharm.
Nanotechnol. 4, 82–89.
Admassu, H., Gasmalla, M.A.A., Yang, R., Zhao, W., 2018. Bioactive peptides derived
from seaweed protein and their health benefits: antihypertensive, antioxidant, and
antidiabetic properties. J. Food Sci. 83, 6–16.
Ahirwar, A., Meignen, G., Khan, M., Khan, N., Rai, A., Schoefs, B., Marchand, J.,
Varjani, S., Vinayak, V., 2021a. Nanotechnological approaches to disrupt the rigid
A. Ahirwar et al.
cell walled microalgae grown in wastewater for value-added biocompounds:
commercial applications, challenges, and breakthrough. Biomass Convers. Biorefin.
1–26.
Ahirwar, A., Meignen, G., Khan, M.J., Sirotiya, V., Scarsini, M., Roux, S., Marchand, J.,
Schoefs, B., Vinayak, V., 2021b. Light modulates transcriptomic dynamics
upregulating astaxanthin accumulation in Haematococcus: a review. Bioresour.
Technol., 125707
Ajibade, F.O., Adelodun, B., Lasisi, K.H., Fadare, O.O., Ajibade, T.F., Nwogwu, N.A.,
Sulaymon, I.D., Ugya, A.Y., Wang, H.C., Wang, A., 2021. Environmental pollution
and their socioeconomic impacts. Microbe Mediated Remediation of Environmental
Contaminants. Elsevier, pp. 321–354.
Alam, M., Parra-Saldivar, R., Bilal, M., Afroze, C.A., Ahmed, M., Iqbal, H., Xu, J., 2021.
Algae-derived bioactive molecules for the potential treatment of sars-cov-2.
Molecules 26, 2134.
Alexandre, K.B., Gray, E.S., Pantophlet, R., Moore, P.L., McMahon, J.B., Chakauya, E.,
O’Keefe, B.R., Chikwamba, R., Morris, L., 2011. Binding of the mannose-specific
lectin, griffithsin, to HIV-1 gp120 exposes the CD4-binding site. J. Virol. 85,
9039–9050.
Ali, I., Alharbi, O.M., 2020. COVID-19: disease, management, treatment, and social
impact. Sci. Total Environ. 728, 138861.
Ali, M., Kim, D.H., Seong, S.H., Kim, H.-R., Jung, H.A., Choi, J.S., 2017. α-Glucosidase
and protein tyrosine phosphatase 1B inhibitory activity of plastoquinones from
marine brown alga Sargassum serratifolium. Mar. Drugs 15, 368.
Ana, P., Nathalie, B., Gilles, B., Daniel, R., Tomas, M.-S., Yolanda, F.-P., 2021. Anti-
Herpes simplex virus (HSV-1) activity and antioxidant capacity of carrageenan-rich
enzymatic extracts from Solieria filiformis (Gigartinales, Rhodophyta). Int. J. Biol.
Macromol. 168, 322–330.
Anti, A., Siregar, R.R., Sipahutar, Y.H., Permadi, A., Siregar, A.N., Salampessy, R.B.,
Sujuliyani, S., Nurbani, S.Z., Purnamasari, H.B., 2021. Antibacterial potential of
symbiont bacteria of brown algae (Turbinaria conoides) obtained from Indonesian
waters. Biodivers. J. Biol. Divers. 22.
Arlov, Ø., Rütsche, D., Asadi Korayem, M., Öztürk, E., Zenobi-Wong, M., 2021.
Engineered sulfated polysaccharides for biomedical applications. Adv. Funct. Mater.
31, 2010732.
Aw, M.S., Simovic, S., Addai-Mensah, J., Losic, D., 2011. Silica microcapsules from
diatoms as new carrier for delivery of therapeutics. Nanomed. (Lond., Engl. ) 6,
1159–1173.
Aziz, E., Batool, R., Khan, M.U., Rauf, A., Akhtar, W., Heydari, M., Rehman, S.,
Shahzad, T., Malik, A., Mosavat, S.H., Plygun, S., Shariati, M.A., 2020. An overview
on red algae bioactive compounds and their pharmaceutical applications.
J. Complement. Integr. Med.
Banerjee, A., Kumar, N., Varjani, S.J., Guria, C., Bandopadhyay, R., Shukla, P.,
Banerjee, C., 2018. Computational modelling and prediction of microalgae growth
focused towards improved lipid production. Biosynthetic technology and
environmental challenges. Springer, pp. 223–232.
Barbosa, M., Lopes, G., Ferreres, F., Andrade, P.B., Pereira, D.M., Gil-Izquierdo, Á.,
Valentão, P., 2017. Phlorotannin extracts from Fucales: marine polyphenols as
bioregulators engaged in inflammation-related mediators and enzymes. Algal Res.
28, 1–8.
Barkia, I., Saari, N., Manning, S.R., 2019. Microalgae for high-value products towards
human health and nutrition. Mar. Drugs 17.
Barre, A., Simplicien, M., Benoist, H., Van Damme, E.J., Rougé, P., 2019. Mannose-
specific lectins from marine algae: diverse structural scaffolds associated to common
virucidal and anti-cancer properties. Mar. Drugs 17, 440.
Barredo, J.L., García-Estrada, C., Kosalkova, K., Barreiro, C., 2017. Biosynthesis of
astaxanthin as a main carotenoid in the heterobasidiomycetous yeast
Xanthophyllomyces dendrorhous. J. Fungi 3, 44.
Beaulieu, L., Bondu, S., Doiron, K., Rioux, L.-E., Turgeon, S.L., 2015. Characterization of
antibacterial activity from protein hydrolysates of the macroalga Saccharina
longicruris and identification of peptides implied in bioactivity. J. Funct. Foods 17,
685–697.
Besednova, N.N., Zvyagintseva, T.N., Kuznetsova, T.A., Makarenkova, I.D., Smolina, T.P.,
Fedyanina, L.N., Kryzhanovsky, S.P., Zaporozhets, T.S., 2019. Marine algae
metabolites as promising therapeutics for the prevention and treatment of HIV/
AIDS. Metabolites 9, 87.
Besednova, N.N., Andryukov, B.G., Zaporozhets, T.S., Kryzhanovsky, S.P., Kuznetsova, T.
A., Fedyanina, L.N., Makarenkova, I.D., Zvyagintseva, T.N., 2020. Algae
polyphenolic compounds and modern antibacterial strategies: current achievements
and immediate prospects. Biomedicines 8, 342.
Besednova, N.N., Andryukov, B.G., Zaporozhets, T.S., Kryzhanovsky, S.P., Fedyanina, L.
N., Kuznetsova, T.A., Zvyagintseva, T.N., Shchelkanov, M.Y., 2021. Antiviral effects
of polyphenols from marine algae. Biomedicines 9, 200.
Bhattacharya, D., Price, D.C., 2020. The algal tree of life from a genomics perspective.
Photosynthesis in Algae: Biochemical and Physiological Mechanisms. Springer,
pp. 11–24.
Bjarnadóttir, M., Aðalbjörnsson, B.V., Nilsson, A., Slizyte, R., Roleda, M.Y.,
Hreggviðsson, G.Ó., Friðjónsson, Ó.H., Jónsdóttir, R., 2018. Palmaria palmata as an
alternative protein source: enzymatic protein extraction, amino acid composition,
and nitrogen-to-protein conversion factor. J. Appl. Phycol. 30, 2061–2070.
Boominathan, M., Mahesh, A., 2015. Seaweed Carotenoids for Cancer Therapeutics.
Handbook of Anticancer Drugs from Marine Origin. Springer, pp. 185–203.
Brodie, J., Andersen, R., Kawachi, M., Millar, A., 2009. Endangered algae and how to
protect them. Phycologia 48, 423–438.
Butler, T., Kapoore, R.V., Vaidyanathan, S., 2020. Phaeodactylum tricornutum: a diatom
cell factory. Trends Biotechnol. 38, 606–622.
43
Journal of Biotechnology 349 (2022) 32–46
Cao, L., Iris, K., Cho, D.-W., Wang, D., Tsang, D.C., Zhang, S., Ding, S., Wang, L., Ok, Y.S.,
2019. Microwave-assisted low-temperature hydrothermal treatment of red seaweed
(Gracilaria lemaneiformis) for production of levulinic acid and algae hydrochar.
Bioresour. Technol. 273, 251–258.
Carballo-Cárdenas, E.C., Tuan, P.M., Janssen, M., Wijffels, R.H., 2003. Vitamin E
(α-tocopherol) production by the marine microalgae Dunaliella tertiolecta and
Tetraselmis suecica in batch cultivation. Biomol. Eng. 20, 139–147.
Carpine, R., Sieber, S., 2021. Antibacterial and antiviral metabolites from cyanobacteria:
their application and their impact on human health. Curr. Res. Biotechnol.
Çelebi, H. , Bahadır, T. , Şimşek, İ. , Tulun, Ş. , 2021. Use of Dunaliella salina in
Environmental Applications.
Cepas, V., Gutiérrez-Del-Río, I., López, Y., Redondo-Blanco, S., Gabasa, Y., Iglesias, M.J.,
Soengas, R., Fernández-Lorenzo, A., López-Ibáñez, S., Villar, C.J., 2021. Microalgae
and cyanobacteria strains as producers of lipids with antibacterial and antibiofilm
activity. Mar. Drugs 19, 675.
Chakdar, H., Pabbi, S., 2017. Chapter 9 - algal pigments for human health and
cosmeceuticals. In: Rastogi, R.P., Madamwar, D., Pandey, A. (Eds.), Algal Green
Chemistry. Elsevier, Amsterdam, pp. 171–188.
Chen, J., Li, H., Zhao, Z., Xia, X., Li, B., Zhang, J., Yan, X., 2018. Diterpenes from the
marine algae of the genus Dictyota. Mar. Drugs 16, 159.
Chen, X., Ni, L., Fu, X., Wang, L., Duan, D., Huang, L., Xu, J., Gao, X., 2021. Molecular
mechanism of anti-inflammatory activities of a novel sulfated galactofucan from
saccharina japonica. Mar. Drugs 19, 430.
Chew, K.W., Khoo, K.S., Foo, H.T., Chia, S.R., Walvekar, R., Lim, S.S., 2021. Algae
utilization and its role in the development of green cities. Chemosphere 268,
129322.
Chia, W.Y., Kok, H., Chew, K.W., Low, S.S., Show, P.L., 2021. Can algae contribute to the
war with Covid-19? Bioengineered 12, 1226–1237.
Cindana F.R., Mo’o, Wilar, G., Devkota, H.P., Wathoni, N., 2020. Ulvan, a polysaccharide
from macroalga Ulva sp.: a review of chemistry, biological activities and potential
for food and biomedical applications. Appl. Sci. 10, 5488.
Cirne-Santos, C.C., Barros, Cd.S., Gomes, M.W., Gomes, R., Cavalcanti, D.N., Obando, J.
M., Ramos, C.J., Villaça, R.C., Teixeira, V.L., Paixão, I.Cd.P., 2019a. In vitro antiviral
activity against zika virus from a natural product of the Brazilian brown seaweed
Dictyota menstrualis. Nat. Prod. Commun. 14, 1934578X19859128.
Cirne-Santos, C.C., Barros, Cd.S., Nogueira, C.C.R., Azevedo, R.C., Yamamoto, K.A.,
Meira, G.L.S., Vasconcelos, Z.F.Md, Ratcliffe, N.A., Teixeira, V.L., Schmidt-
Chanasit, J., 2019b. Inhibition by marine algae of chikungunya virus isolated from
patients in a recent disease outbreak in Rio de Janeiro. Front. Microbiol. 10, 2426.
D’Silva, M.S., Anil, A.C., Naik, R.K., D’Costa, P.M., 2012. Algal blooms: a perspective
from the coasts of India. Nat. Hazards 63, 1225–1253.
Davis, E.H., Beck, A.S., Li, L., White, M.M., Greenberg, M.B., Thompson, J.K., Widen, S.
G., Barrett, A.D., Bourne, N., 2021. Japanese encephalitis virus live attenuated
vaccine strains display altered immunogenicity, virulence and genetic diversity. NPJ
Vaccin. 6, 1–14.
Decho, A.W., Gutierrez, T., 2017. Microbial extracellular polymeric substances (EPSs) in
ocean systems. Front. Microbiol. 8, 922.
Decker, J.S., Menacho-Melgar, R., Lynch, M.D., 2020. Low-cost, large-scale production of
the anti-viral lectin griffithsin. Front. Bioeng. Biotechnol. 8, 1020.
Dellatorre, F.G., Avaro, M.G., Commendatore, M.G., Arce, L., de Vivar, M.E.D., 2020. The
macroalgal ensemble of Golfo Nuevo (Patagonia, Argentina) as a potential source of
valuable fatty acids for nutritional and nutraceutical purposes. Algal Res. 45,
101726.
Deniz, I., García-Vaquero, M., Imamoglu, E., 2017. Trends in red biotechnology:
microalgae for pharmaceutical applications. Microalgae-based Biofuels and
Bioproducts. Elsevier, pp. 429–460.
Devda, V., Chaudhary, K., Varjani, S., Pathak, B., Patel, A.K., Singhania, R.R.,
Taherzadeh, M.J., Ngo, H.H., Wong, J.W., Guo, W., Chaturvedi, P., 2021. Recovery
of resources from industrial wastewater employing electrochemical technologies:
status, advancements and perspectives. Bioengineered 12 (1), 4697–4718.
Ehsan, U., Liao, Q.V., Muller, M., Riedl, M.O., Weisz, J.D., 2021. Expanding
explainability: Towards social transparency in ai systems. Proceedings of the 2021
CHI Conference on Human Factors in Computing Systems, pp. 1–19.
Ehuwa, O., Jaiswal, A.K., Jaiswal, S., 2021. Salmonella, food safety and food handling
practices. Foods 10, 907.
El-Hossary, E.M., Cheng, C., Hamed, M.M., Hamed, A.N.E.-S., Ohlsen, K., Hentschel, U.,
Abdelmohsen, U.R., 2017. Antifungal potential of marine natural products. Eur. J.
Med. Chem. 126, 631–651.
Ercolano, G., De Cicco, P., Ianaro, A., 2019. New drugs from the sea: pro-apoptotic
activity of sponges and algae derived compounds. Mar. Drugs 17, 31.
Ezzat, S.M., Bishbishy, M.H.E., Habtemariam, S., Salehi, B., Sharifi-Rad, M., Martins, N.,
Sharifi-Rad, J., 2018. Looking at marine-derived bioactive molecules as upcoming
anti-diabetic agents: a special emphasis on PTP1B inhibitors. Molecules 23, 3334.
Fernando, I.S., Jayawardena, T.U., Kim, H.-S., Lee, W.W., Vaas, A., De Silva, H.,
Abayaweera, G., Nanayakkara, C., Abeytunga, D., Lee, D.-S., 2019. Beijing urban
particulate matter-induced injury and inflammation in human lung epithelial cells
and the protective effects of fucosterol from Sargassum binderi (Sonder ex J.
Agardh). Environ. Res. 172, 150–158.
Fischer, K., Nguyen, K., LiWang, P.J., 2020. Griffithsin retains anti-HIV-1 potency with
changes in gp120 glycosylation and complements broadly neutralizing antibodies
PGT121 and PGT126. Antimicrob. Agents Chemother. 64 e01084-01019.
Frediansyah, S.S.A., 2021. The antiviral activity of iota-, kappa-, and lambda-
carrageenan against COVID-19: a critical review. Clin. Epidemiol. Glob. Health,
100826.
A. Ahirwar et al.
Freitas, F., Torres, C.A., Araújo, D., Farinha, I., Pereira, J.R., Concórdio-Reis, P., Reis, M.
A., 2021. Advanced microbial polysaccharides. Biopolym. Biomed. Biotechnol. Appl.
19–62.
García-Vaquero, M., Rajauria, G., O’Doherty, J.V., Sweeney, T., 2017. Polysaccharides
from macroalgae: recent advances, innovative technologies and challenges in
extraction and purification. Food Res. Int. 99, 1011–1020.
Garrison, A.R., Giomarelli, B.G., Lear-Rooney, C.M., Saucedo, C.J., Yellayi, S., Krumpe, L.
R., Rose, M., Paragas, J., Bray, M., Olinger Jr., G.G., 2014. The cyanobacterial lectin
scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus.
Antivir. Res. 112, 1–7.
Gautam, S., Pandey, L.K., Vinayak, V., Arya, A., 2017. Morphological and physiological
alterations in the diatom Gomphonema pseudoaugur due to heavy metal stress. Ecol.
Indic. 72, 67–76.
Geetha Bai, R., Tuvikene, R., 2021. Potential antiviral properties of industrially
important marine algal polysaccharides and their significance in fighting a future
viral pandemic. Viruses 13, 1817.
Golke, P., Hönemann, M., Bergs, S., Liebert, U.G., 2021. Human rhinoviruses in adult
patients in a tertiary care hospital in germany: molecular epidemiology and clinical
significance. Viruses 13, 2027.
Graham, J.M., Graham, L.E., Zulkifly, S.B., Pfleger, B.F., Hoover, S.W., Yoshitani, J.,
2012. Freshwater diatoms as a source of lipids for biofuels. J. Ind. Microbiol.
Biotechnol. 39, 419–428.
Grosshagauer, S., Kraemer, K., Somoza, V., 2020. The true value of Spirulina. J. Agric.
Food Chem. 68, 4109–4115.
Guiry, M.D., 2012. How many species of algae are there? J. Phycol. 48, 1057–1063.
Gupta, A.K., Seth, K., Maheshwari, K., Baroliya, P.K., Meena, M., Kumar, A., Vinayak, V.,
2021. Biosynthesis and extraction of high-value carotenoid from algae. Front. Biosci.
26, 171–190.
Gupta, S., Kashyap, M., Kumar, V., Jain, P., Vinayak, V., Joshi, K.B., 2018. Peptide
mediated facile fabrication of silver nanoparticles over living diatom surface and its
application. J. Mol. Liq. 249, 600–608.
Gutiérrez-Rodríguez, A.G., Juárez-Portilla, C., Olivares-Bañuelos, T., Zepeda, R.C., 2018.
Anticancer activity of seaweeds. Drug Discov. Today 23, 434–447.
Guzmán, F., Wong, G., Román, T., Cárdenas, C., Alvárez, C., Schmitt, P., Albericio, F.,
Rojas, V., 2019. Identification of antimicrobial peptides from the microalgae
Tetraselmis suecica (Kylin) Butcher and bactericidal activity improvement. Mar.
Drugs 17, 453.
Hannan, M., Faisal, M., Ker, P.J., Begum, R., Dong, Z., Zhang, C., 2020. Review of
optimal methods and algorithms for sizing energy storage systems to achieve
decarbonization in microgrid applications. Renew. Sustain. Energy Rev. 131,
110022.
Hans, N., Malik, A., Naik, S., 2020. Antiviral activity of sulfated polysaccharides from
marine algae and its application in combating COVID-19: mini review. Bioresour.
Technol. Rep., 100623
Hans, N., Malik, A., Naik, S., 2021. Antiviral activity of sulfated polysaccharides from
marine algae and its application in combating COVID-19: mini review. Bioresour.
Technol. Rep. 13, 100623.
Harwood, J.L., 2019. Algae: critical sources of very long-chain polyunsaturated fatty
acids. Biomolecules 9, 708.
Herath, K.H.I.N.M., Kim, H.J., Mihindukulasooriya, S.P., Kim, A., Kim, H.J., Jeon, Y.-J.,
Jee, Y., 2020. Sargassum horneri extract containing mojabanchromanol attenuates
the particulate matter exacerbated allergic asthma through reduction of Th2 and
Th17 response in mice. Environ. Pollut. 265, 114094.
Hossain, M.S., Khan, M.A.A.M., Sanjana, J.M., Kibria, K.K., (2021) Antibacterial actions
of fatty acids isolated from marine algae: An in vitro evidence-based review.
Huang, W., Daboussi, F., 2017. Genetic and metabolic engineering in diatoms. Philos.
Trans. R. Soc. Lond. Ser. B Biol. Sci. 372.
Hussein, H.A., Abdullah, M.A., 2020. Anticancer compounds derived from marine
diatoms. Mar. Drugs 18, 356.
Iravani, S., Varma, R.S., 2021. Important roles of oligo-and polysaccharides against
SARS-CoV-2: recent advances. Appl. Sci. 11, 3512.
Ismail, G.A., El-Sheekh, M.M., Samy, R.M., Gheda, S.F., 2021. Antimicrobial,
antioxidant, and antiviral activities of biosynthesized silver nanoparticles by
phycobiliprotein crude extract of the cyanobacteria spirulina platensis and nostoc
linckia. BioNanoScience 11, 355–370.
Jabeen, M., Dutot, M., Fagon, R., Verrier, B., Monge, C., 2021. Seaweed sulfated
polysaccharides against respiratory viral infections. Pharmaceutics 13, 733.
Jain, A., Patel, N.B., Tailor, V., Sathvara, S., Kalasariya, H.S., 2020 AN APPRAISAL ON
ANTIMICROBIAL APPLICABILITY OF MARINE MACROALGAE.
Janahi, E.M.A., Haque, S., Akhter, N., Wahid, M., Jawed, A., Mandal, R.K., Lohani, M.,
Areeshi, M.Y., Almalki, S., Das, S., 2018. Bioengineered intravaginal isolate of
lactobacillus plantarum expresses algal lectin scytovirin demonstrating anti-HIV-1
activity. Microb. Pathog. 122, 1–6.
Jayawardena, T.U., Sanjeewa, K., Nagahawatta, D., Lee, H.-G., Lu, Y.-A., Vaas, A.,
Abeytunga, D., Nanayakkara, C., Lee, D.-S., Jeon, Y.-J., 2020. Anti-Inflammatory
effects of sulfated polysaccharide from Sargassum swartzii in macrophages via
blocking TLR/NF-Κb signal transduction. Mar. Drugs 18, 601.
Jin, W., Tang, H., Zhang, J., Wei, B., Sun, J., Zhang, W., Zhang, F., Wang, H., Linhardt, R.
J., Zhong, W., 2020. Structural analysis of a novel sulfated galacto-fuco-xylo-
glucurono-mannan from Sargassum fusiforme and its anti-lung cancer activity. Int. J.
Biol. Macromol. 149, 450–458.
Kabir, A., Nazeer, N., Bissessur, R., Ahmed, M., 2020. Diatoms embedded, self-assembled
carriers for dual delivery of chemotherapeutics in cancer cell lines. Int. J. Pharm.
573, 118887.
44
Journal of Biotechnology 349 (2022) 32–46
Kartik, A., Akhil, D., Lakshmi, D., Gopinath, K.P., Arun, J., Sivaramakrishnan, R.,
Pugazhendhi, A., 2021. A critical review on production of biopolymers from algae
biomass and their applications. Bioresour. Technol., 124868
Keshri, J.P., 2012. Algae in medicine. Med. Plant. Var. Perspect. 31–50.
Khan, M.J., Singh, R., Shewani, K., Shukla, P., Bhaskar, P., Joshi, K.B., Vinayak, V., 2020.
Exopolysaccharides directed embellishment of diatoms triggered on plastics and
other marine litter. Sci. Rep. 10, 1–11.
Khan, M.J., Mangesh, H., Ahirwar, A., Schoefs, B., Pugazhendhi, A., Varjani, S.,
Rajendran, K., Bhatia, S.K., Saratale, G.D., Saratale, R.G., 2021. Insights into diatom
microalgal farming for treatment of wastewater and pretreatment of algal cells by
ultrasonication for value creation. Environ. Res., 111550
Kidgell, J.T., Magnusson, M., de Nys, R., Glasson, C.R., 2019. Ulvan: a systematic review
of extraction, composition and function. Algal Res. 39, 101422.
Kini, S., Divyashree, M., Mani, M.K., Mamatha, B.S., 2020. Algae and cyanobacteria as a
source of novel bioactive compounds for biomedical applications. Advances in
Cyanobacterial Biology. Elsevier, pp. 173–194.
Kiran, B.R., Venkata Mohan, S., 2021. Microalgal cell biofactory—therapeutic,
nutraceutical and functional food applications. Plants 10, 836.
Kora, A.J., Rastogi, L., 2018. Green synthesis of palladium nanoparticles using gum
ghatti (Anogeissus latifolia) and its application as an antioxidant and catalyst. Arab.
J. Chem. 11, 1097–1106.
Krishnan, S., Jeevanandam, J., Acquah, C., Danquah, M.K., 2021. Extraction of algal
neutral lipids for biofuel production. Biodiesel Fuels Based on Edible and Nonedible
Feedstocks, Wastes, and Algae. CRC Press, pp. 785–802.
Krylova, N.V., Ermakova, S.P., Lavrov, V.F., Leneva, I.A., Kompanets, G.G., Iunikhina, O.
V., Nosik, M.N., Ebralidze, L.K., Falynskova, I.N., Silchenko, A.S., 2020. The
comparative analysis of antiviral activity of native and modified fucoidans from
brown algae Fucus evanescens in vitro and in vivo. Mar. Drugs 18, 224.
Kwon, P.S., Oh, H., Kwon, S.-J., Jin, W., Zhang, F., Fraser, K., Hong, J.J., Linhardt, R.J.,
Dordick, J.S., 2020. Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro.
Cell Discov. 6, 1–4.
Laurienzo, P., 2010. Marine polysaccharides in pharmaceutical applications: an
overview. Mar. Drugs 8, 2435–2465.
Le, P.U., Vo, T.S., Kim, S.K., 2020. Marine cyanobacteria: applications in food, energy,
and pharmaceuticals. Encycl. Mar. Biotechnol. 4, 2161–2171.
Lee, C., 2019. Griffithsin, a highly potent broad-spectrum antiviral lectin from red algae:
from discovery to clinical application. Mar. Drugs 17, 567.
Lee, W.-K., Ho, C.-L., 2021. Ecological and evolutionary diversification of sulphated
polysaccharides in diverse photosynthetic lineages: a review. Carbohydr. Polym.,
118764
Li, Y., Sun, S., Pu, X., Yang, Y., Zhu, F., Zhang, S., Xu, N., 2018. Evaluation of
antimicrobial activities of seaweed resources from Zhejiang Coast, China.
Sustainability 10, 2158.
Li-Beisson, Y., Thelen, J.J., Fedosejevs, E., Harwood, J.L., 2019. The lipid biochemistry of
eukaryotic algae. Prog. Lipid Res. 74, 31–68.
Liu, L., Pohnert, G., Wei, D., 2016. Extracellular metabolites from industrial microalgae
and their biotechnological potential. Mar. Drugs 14, 191.
Lo, M.K., Spengler, J.R., Krumpe, L.R., Welch, S.R., Chattopadhyay, A., Harmon, J.R.,
Coleman-McCray, J.D., Scholte, F.E., Hotard, A.L., Fuqua, J.L., 2020. Griffithsin
inhibits Nipah virus entry and fusion and can protect syrian golden Hamsters from
lethal Nipah virus challenge. J. Infect. Dis. 221, S480–S492.
Lopes, N., Ray, S., Espada, S.F., Bomfim, W.A., Ray, B., Faccin-Galhardi, L.C., Linhares, R.
E.C., Nozawa, C., 2017. Green seaweed Enteromorpha compressa (Chlorophyta,
Ulvaceae) derived sulphated polysaccharides inhibit herpes simplex virus. Int. J.
Biol. Macromol. 102, 605–612.
Mader, J., Gallo, A., Schommartz, T., Handke, W., Nagel, C.-H., Günther, P., Brune, W.,
Reich, K., 2016. Calcium spirulan derived from Spirulina platensis inhibits herpes
simplex virus 1 attachment to human keratinocytes and protects against herpes
labialis. J. Allergy Clin. Immunol. 137, 197–203 e193.
Magda, F., Deyab, M.A., El-Shanawany, R.S., Abu-Ahmed, S.E., 2021. Fatty acids of
Cladophora glomerata and Chaetomorpha vieillardii (Cladophoraceae) of different
niches inhibit the pathogenic microbial growth. Aquat. Bot., 103461
Malviya, S., Scalco, E., Audic, S., Vincent, F., Veluchamy, A., Poulain, J., Wincker, P.,
Iudicone, D., de Vargas, C., Bittner, L., Zingone, A., Bowler, C., 2016. Insights into
global diatom distribution and diversity in the world’s ocean. Proc. Natl. Acad. Sci.
USA 113, E1516–E1525.
Martínez Andrade, K.A., Lauritano, C., Romano, G., Ianora, A., 2018. Marine microalgae
with anti-cancer properties. Mar. Drugs 16.
Maulucci, G., Cohen, O., Daniel, B., Sansone, A., Petropoulou, P., Filou, S.,
Spyridonidis, A., Pani, G., De Spirito, M., Chatgilialoglu, C., 2016. Fatty acid-related
modulations of membrane fluidity in cells: detection and implications. Free Radic.
Res. 50, S40–S50.
Mehta, P., Singh, D., Saxena, R., Rani, R., Gupta, R.P., Puri, S.K., Mathur, A.S., 2018.
High-value coproducts from algae—an innovational way to deal with advance algal
industry. Waste to wealth. Springer,, pp. 343–363.
Messina, C.M., Renda, G., Laudicella, V.A., Trepos, R., Fauchon, M., Hellio, C.,
Santulli, A., 2019. From ecology to biotechnology, study of the defense strategies of
algae and halophytes (from Trapani Saltworks, NW Sicily) with a focus on
antioxidants and antimicrobial properties. Int. J. Mol. Sci. 20, 881.
Mickymaray, S., Alturaiki, W., 2018. Antifungal efficacy of marine macroalgae against
fungal isolates from bronchial asthmatic cases. Molecules 23, 3032.
Milito, A., Orefice, I., Smerilli, A., Castellano, I., Napolitano, A., Brunet, C., Palumbo, A.,
2020. Insights into the light response of skeletonema marinoi: involvement of
ovothiol. Mar. Drugs 18, 477.
A. Ahirwar et al.
Mišurcová, L., Buňka, F., Ambrožová, J.V., Machů, L., Samek, D., Kráčmar, S., 2014.
Amino acid composition of algal products and its contribution to RDI. Food Chem.
151, 120–125.
Mishra, B., Varjani, S., Kumar, G., Awasthi, M.K., Awasthi, S.K., Sindhu, R., Binod, P.,
Rene, E.R., Zhang, Z., 2021. Microbial approaches for remediation of pollutants:
innovations, future outlook, and challenges. Energy & Environment 32 (6),
1029–1058.
Monje-Galvan, V., Klauda, J.B., 2017. Two sterols, two bilayers: insights on membrane
structure from molecular dynamics. Mol. Simul. 43, 1179–1188.
Munir, R., Lisec, J., Swinnen, J.V., Zaidi, N., 2019. Lipid metabolism in cancer cells
under metabolic stress. Br. J. Cancer 120, 1090–1098.
Muro, E., Atilla-Gokcumen, G.E., Eggert, U.S., 2014. Lipids in cell biology: how can we
understand them better? Mol. Biol. Cell 25, 1819–1823.
Nagarajan, D., Varjani, S., Lee, D.-J., Chang, J.-S., 2021. Sustainable aquaculture and
animal feed from microalgae–Nutritive value and techno-functional components.
Renew. Sustain. Energy Rev. 150, 111549.
Nguyen, T.-T., Bui, X.-T., Ngo, H.H., Nguyen, K.-Q., Nguyen, H.-H., Némery, J.,
Fujioka, T., Duong, C.H., Dang, B.-T., Varjani, S., 2021. Nutrient recovery and
microalgae biomass production from urine by membrane photobioreactor at low
biomass retention times. Sci. Total Environ. 785, 147423.
Ogawa, Y., Kimura, S., Wada, M., 2011. Electron diffraction and high-resolution imaging
on highly-crystalline β-chitin microfibril. J. Struct. Biol. 176, 83–90.
Ouyang, Y., Qiu, Y., Liu, Y., Zhu, R., Chen, Y., El-Seedi, H.R., Chen, X., Zhao, C., 2021.
Cancer-fighting potentials of algal polysaccharides as nutraceuticals. Food Res. Int.
147, 110522.
Pagarete, A., Ramos, A.S., Puntervoll, P., Allen, M.J., Verdelho, V., 2021. Antiviral
potential of algal metabolites—a comprehensive review. Mar. Drugs 19, 94.
Paiva, L., Lima, E., Neto, A.I., Baptista, J., 2017. Angiotensin I-converting enzyme (ACE)
inhibitory activity, antioxidant properties, phenolic content and amino acid profiles
of Fucus spiralis L. protein hydrolysate fractions. Mar. Drugs 15, 311.
Pangestuti, R., Suryaningtyas, I.T., Siahaan, E.A., Kim, S.-K., 2020. Cosmetics and
cosmeceutical applications of microalgae pigments. Pigments from Microalgae
Handbook. Springer, pp. 611–633.
Parajuli, B., Acharya, K., Bach, H.C., Parajuli, B., Zhang, S., Smith III, A.B., Abrams, C.F.,
Chaiken, I., 2018. Restricted HIV-1 Env glycan engagement by lectin-reengineered
DAVEI protein chimera is sufficient for lytic inactivation of the virus. Biochem. J.
475, 931–957.
Parsaeimehr, A., Chen, Y.-F., 2013. Algal bioactive diversities against pathogenic
microbes. Microbiol pathogens and strategies for combating them: science. Technol.
Educ. 796–803.
Pendyala, B., Patras, A., Dash, C., 2021. Phycobilins as potent food bioactive broad-
spectrum inhibitors against proteases of SARS-CoV-2 and other coronaviruses: a
preliminary study. Front. Microbiol. 12.
Pereira, A.G., Otero, P., Echave, J., Carreira-Casais, A., Chamorro, F., Collazo, N.,
Jaboui, A., Lourenço-Lopes, C., Simal-Gandara, J., Prieto, M.A., 2021. Xanthophylls
from the sea: algae as source of bioactive carotenoids. Mar. Drugs 19, 188.
Pereira, L., 2018. Therapeutic and Nutritional Uses of Algae. CRC Press.
Pérez, M.J., Falqué, E., Domínguez, H., 2016. Antimicrobial action of compounds from
marine seaweed. Mar. Drugs 14, 52.
Petit, L., Vernès, L., Cadoret, J.-P., 2021. Docking and in silico toxicity assessment of
Arthrospira compounds as potential antiviral agents against SARS-CoV-2. J. Appl.
Phycol. 1–24.
Pierella Karlusich, J.J., Bowler, C., Biswas, H., 2021. Carbon dioxide concentration
mechanisms in natural populations of marine diatoms: insights from Tara Oceans.
Front. Plant Sci. 12, 659.
Piersma, S.J., Poursine-Laurent, J., Yang, L., Barber, G.N., Parikh, B.A., Yokoyama, W.M.,
2020. Virus infection is controlled by hematopoietic and stromal cell sensing of
murine cytomegalovirus through STING. Elife 9, e56882.
Pina-Pérez, M.C., Rivas, A., Martínez, A., Rodrigo, D., 2017. Antimicrobial potential of
macro and microalgae against pathogenic and spoilage microorganisms in food.
Food Chem. 235, 34–44.
Pino-Cortés, E., Díaz-Robles, L.A., Cubillos, F., Cereceda-Balic, F., Santander, R., Fu, J.S.,
Carrasco, S., Acosta, J., 2021. The black carbon dispersion in the Southern
Hemisphere and its transport and fate to Antarctica, an Anthropocene evidence for
climate change policies. Sci. Total Environ. 778, 146242.
Piwowar, A., Harasym, J., 2020. The importance and prospects of the use of algae in
agribusiness. Sustainability 12, 5669.
Pohl, P., Zurheide, F., 2019. Fat Production in Freshwater and Marine Algae, Vol. 2. De
Gruyter, pp. 65–80.
Popa, G.L., Papa, M.I., 2021. Salmonella spp. infection-a continuous threat worldwide.
Germs 11, 88.
Pradhan, B., Nayak, R., Patra, S., Jit, B.P., Ragusa, A., Jena, M., 2021. Bioactive
metabolites from marine algae as potent pharmacophores against oxidative stress-
associated human diseases: a comprehensive review. Molecules 26, 37.
Raja, A., Vipin, C., Aiyappan, A., 2013. Biological importance of marine algae-an
overview. Int. J. Curr. Microbiol. Appl. Sci. 2, 222–227.
Rathna, R., Nakkeeran, E., Varjani, S., Madhumitha, B., 2019. Intriguing disposition of
marine algae-derived enzymes in food biotechnology. Green Bio-processes. Springer,
pp. 305–321.
Ray, B., Ali, I., Jana, S., Mukherjee, S., Pal, S., Ray, S., Schütz, M., Marschall, M., 2022.
Antiviral strategies using natural source-derived sulfated polysaccharides in the light
of the COVID-19 pandemic and major human pathogenic viruses. Viruses 14, 35.
Rayapu, L., Chakraborty, K., Valluru, L., 2021. Marine algae as a potential source for
anti-diabetic compounds-a brief review. Curr. Pharm. Des. 27, 789–801.
45
Journal of Biotechnology 349 (2022) 32–46
Reis, R.P., de Carvalho Junior, A.A., Facchinei, A.P., dos Santos Calheiros, A.C.,
Castelar, B., 2018. Direct effects of ulvan and a flour produced from the green alga
Ulva fasciata Delile on the fungus Stemphylium solani Weber. Algal Res. 30, 23–27.
Richards, C., Williams, N.A., Fitton, J.H., Stringer, D.N., Karpiniec, S.S., Park, A.Y., 2020.
Oral fucoidan attenuates lung pathology and clinical signs in a severe influenza a
mouse model. Mar. Drugs 18, 246.
Righini, H., Baraldi, E., García Fernández, Y., Martel Quintana, A., Roberti, R., 2019.
Different antifungal activity of anabaena sp., Ecklonia sp., and Jania sp. against
Botrytis cinerea. Mar. Drugs 17, 299.
Rivera-Rondón, C.A., Catalan, J., 2020. Diatoms as indicators of the multivariate
environment of mountain lakes. Sci. Total Environ. 703, 135517.
Rojas, V., Rivas, L., Cárdenas, C., Guzmán, F., 2020. Cyanobacteria and eukaryotic
microalgae as emerging sources of antibacterial peptides. Molecules 25, 5804.
Rosa, G.P., Tavares, W.R., Sousa, P., Seca, A.M., Pinto, D.C., 2020. Seaweed secondary
metabolites with beneficial health effects: An overview of successes in in vivo studies
and clinical trials. Mar. Drugs 18, 8.
Saini, R.K., Keum, Y.-S., 2018. Carotenoid extraction methods: a review of recent
developments. Food Chem. 240, 90–103.
Sandhya, S., Vijayan, K., 2019. Symbiotic association among marine microalgae and
bacterial flora: a study with special reference to commercially important Isochrysis
galbana culture. J. Appl. Phycol. 31, 2259–2266.
Sanjeewa, K., Jeon, Y.-J., 2021. Fucoidans as scientifically and commercially important
algal polysaccharides. Multidiscip. Digit. Publ. Inst. 284.
Sanjeewa, K.A., Lee, J.-S., Kim, W.-S., Jeon, Y.-J., 2017. The potential of brown-algae
polysaccharides for the development of anticancer agents: An update on anticancer
effects reported for fucoidan and laminaran. Carbohydr. Polym. 177, 451–459.
Saranya, G., Ramachandra, T., 2021. Scope for biodiesel and bioactive compounds
production in the diatom Nitzschia punctata. Fuel 300, 120985.
Saravanan, A., Kumar, P.S., Varjani, S., Jeevanantham, S., Yaashikaa, P., Thamarai, P.,
Abirami, B., George, C.S., 2021. A review on algal-bacterial symbiotic system for
effective treatment of wastewater. Chemosphere, 129540.
Ścieszka, S., Klewicka, E., 2019. Algae in food: a general review. Crit. Rev. Food Sci.
Nutr. 59, 3538–3547.
Seedevi, P., Moovendhan, M., Viramani, S., Shanmugam, A., 2017. Bioactive potential
and structural chracterization of sulfated polysaccharide from seaweed (Gracilaria
corticata). Carbohydr. Polym. 155, 516–524.
Sekar, M., Mathimani, T., Alagumalai, A., Chi, N.T.L., Duc, P.A., Bhatia, S.K.,
Brindhadevi, K., Pugazhendhi, A., 2021. A review on the pyrolysis of algal biomass
for biochar and bio-oil–bottlenecks and scope. Fuel 283, 119190.
Setyorini, H., Puspitasari, A., (2021) Fat, water and ash content in Chlorophyceae,
Rhodophyceae and Phaeophyceae macroalgae at Sepanjang Beach, Yogyakarta,
Indonesia. IOP Conference Series: Earth and Environmental Science. IOP Publishing,
p. 012073.
Shannon, E., Abu-Ghannam, N., 2016. Antibacterial derivatives of marine algae: an
overview of pharmacological mechanisms and applications. Mar. Drugs 14, 81.
Sharifuddin, Y., Chin, Y.-X., Lim, P.-E., Phang, S.-M., 2015. Potential bioactive
compounds from seaweed for diabetes management. Mar. Drugs 13, 5447–5491.
Shehata, A.I., Wang, T., Jibril Habib, Y., Wang, J., Fayed, W.M., Zhang, Z., 2020. The
combined effect of vitamin E, arachidonic acid, Haemtococcus pluvialis, nucleotides
and yeast extract on growth and ovarian development of crayfish (Cherax
quadricarinatus) by the orthogonal array design. Aquac. Nutr. 26, 2007–2022.
Shi, Q., Wang, A., Lu, Z., Qin, C., Hu, J., Yin, J., 2017. Overview on the antiviral activities
and mechanisms of marine polysaccharides from seaweeds. Carbohydr. Res. 453,
1–9.
Shrestha, S., Johnston, M.R., Zhang, W., Smid, S.D., 2021. A phlorotannin isolated from
Ecklonia radiata, Dibenzodioxin-fucodiphloroethol, inhibits neurotoxicity and
aggregation of β-amyloid. Phytomedicine 1, 100125.
Shtaida, N., Khozin-Goldberg, I., Solovchenko, A., Chekanov, K., Didi-Cohen, S., Leu, S.,
Cohen, Z., Boussiba, S., 2014. Downregulation of a putative plastid PDC E1α subunit
impairs photosynthetic activity and triacylglycerol accumulation in nitrogen-starved
photoautotrophic Chlamydomonas reinhardtii. J. Exp. Bot. 65, 6563–6576.
Siahbalaei, R., Kavoosi, G., Noroozi, M., 2021. Manipulation of Chlorella vulgaris
polyunsaturated ω-3 fatty acid profile by supplementation with vegetable amino
acids and fatty acids. Phycol. Res. 69, 116–123.
Silva, A., Delerue-Matos, C., Figueiredo, S.A., Freitas, O.M., 2019. The use of algae and
fungi for removal of pharmaceuticals by bioremediation and biosorption processes: a
review. Water 11, 1555.
Silva, A., Silva, S.A., Lourenço-Lopes, C., Jimenez-Lopez, C., Carpena, M., Gullón, P.,
Fraga-Corral, M., Domingues, V., Barroso, M.F., Simal-Gandara, J., 2020.
Antibacterial use of macroalgae compounds against foodborne pathogens.
Antibiotics 9, 712.
Singh, G., Dal Grande, F., Divakar, P.K., Otte, J., Crespo, A., Schmitt, I., 2017a.
Fungal–algal association patterns in lichen symbiosis linked to macroclimate.
N. Phytol. 214, 317–329.
Singh, R., Parihar, P., Singh, M., Bajguz, A., Kumar, J., Singh, S., Singh, V.P., Prasad, S.
M., 2017b. Uncovering potential applications of cyanobacteria and algal metabolites
in biology, agriculture and medicine: current status and future prospects. Front.
Microbiol. 8, 515.
Singh, R., Khan, M.J., Rane, J., Gajbhiye, A., Vinayak, V., Joshi, K.B., 2020.
Biofabrication of diatom surface by tyrosine-metal complexes: smart
microcontainers to inhibit bacterial growth. ChemistrySelect 5, 3091–3097.
Siqueira, A.S., Lima, A.R.J., de Souza, R.C., Santos, A.S., Vianez, J.Ld.S.G., Gonçalves, E.
C., 2017a. Anti-dengue virus activity of scytovirin and evaluation of point mutation
effects by molecular dynamics and binding free energy calculations. Biochem.
Biophys. Res. Commun. 490, 1033–1038.
A. Ahirwar et al.
Siqueira, A.S., Lima, A.R.J., de Souza, R.C., Santos, A.S., Vianez Júnior, J.Ld.S.G.,
Gonçalves, E.C., 2017b. In silico analysis of the cyanobacterial lectin scytovirin: new
insights into binding properties. Mol. Biol. Rep. 44, 353–358.
de Siqueira Castro, J., Assemany, P.P., de Oliveira Carneiro, A.C., Ferreira, J., de Jesus
Júnior, M.M., de Ávila Rodrigues, F., Calijuri, M.L., 2021. Hydrothermal
carbonization of microalgae biomass produced in agro-industrial effluent: products,
characterization and applications. Sci. Total Environ. 768, 144480.
Sit, N.W., Chan, Y.S., Lai, S., Lim, L.N., Looi, G., Tay, P., Tee, Y., Woon, Y., Khoo, K.S.,
Ong, H.C., 2018. In vitro antidermatophytic activity and cytotoxicity of extracts
derived from medicinal plants and marine algae. J. De. Mycol. Med. 28, 561–567.
Son, M., Lee, M., Sung, G.-H., Lee, T., Shin, Y.S., Cho, H., Lieberman, P.M., Kang, H.,
2013. Bioactive activities of natural products against herpesvirus infection.
J. Microbiol. 51, 545–551.
SonAwAne, S.K., Arya, S.S., 2018. Plant seed proteins: chemistry, technology and
applications. Curr. Res. Nutr. Food Sci. J. 6, 461–469.
Song, S., Peng, H., Wang, Q., Liu, Z., Dong, X., Wen, C., Ai, C., Zhang, Y., Wang, Z.,
Zhu, B., 2020. Inhibitory activities of marine sulfated polysaccharides against SARS-
CoV-2. Food Funct. 11, 7415–7420.
Soria-Herrera, R.J., Dominguez-Gonzalez, K.G., Rumbo-Pino, R., Piña-Lazaro, A.,
Alvarez-Perez, J.J., Rivera-Gutierrez, S., Ponce-Saavedra, J., Ortiz-Alvarado, R.,
Gonzalez-y-Merchand, J.A., Yahuaca-Juarez, B., 2021. Occurrence of
nontuberculous mycobacteria, salmonella, listeria monocytogenes, and
staphylococcus aureus in artisanal unpasteurized cheeses in the State of Michoacan,
Mexico. J. Food Prot. 84, 760–766.
de Souza Barros, C., Garrido, V., Melchiades, V., Gomes, R., Gomes, M.W.L., Teixeira, V.
L., de Palmer Paixão, I.C.N., 2017. Therapeutic efficacy in BALB/C mice of extract
from marine alga Canistrocarpus cervicornis (Phaeophyceae) against herpes simplex
virus type 1. J. Appl. Phycol. 29, 769–773.
Stokes, W., Peirano, G., Matsumara, Y., Nobrega, D., Pitout, J.D., 2021. Population-based
surveillance of Enterobacter cloacae complex causing blood stream infections in a
centralized Canadian region. Eur. J. Clin. Microbiol. Infect. Dis. 1–7.
Stonik, V.A., Stonik, I.V., 2018. Sterol and sphingoid glycoconjugates from microalgae.
Mar. Drugs 16, 514.
Sugiura, Y., Kinoshita, Y., Misumi, S., Yamatani, H., Katsuzaki, H., Hayashi, Y.,
Murase, N., 2021. Correlation between the seasonal variations in phlorotannin
content and the antiallergic effects of the brown alga Ecklonia cava subsp.
stolonifera. Algal Res. 58, 102398.
Susilowati, R., Sabdono, A., Widowati, I., 2015. Isolation and characterization of bacteria
associated with brown algae Sargassum spp. from Panjang Island and their
antibacterial activities. Proc. Environ. Sci. 23, 240–246.
Takaara, T., Sasaki, S., Fujii, M., Ito, H., Masago, Y., Omura, T., 2019. Lectin-stimulated
cellular iron uptake and toxin generation in the freshwater cyanobacterium
Microcystis aeruginosa. Harmful Algae 83, 25–33.
Tang, T., Cao, S., Zhu, B., Li, Q., 2021. Ulvan polysaccharide-degrading enzymes: an
updated and comprehensive review of sources category, property, structure, and
applications of ulvan lyases. Algal Res. 60, 102477.
Tanna, B., Mishra, A., 2018. Metabolites unravel nutraceutical potential of edible
seaweeds: an emerging source of functional food. Compr. Rev. Food Sci. Food Saf.
17, 1613–1624.
Terasawa, M., Hayashi, K., Lee, J.-B., Nishiura, K., Matsuda, K., Hayashi, T.,
Kawahara, T., 2020. Anti-influenza A virus activity of rhamnan sulfate from green
algae Monostroma nitidum in mice with normal and compromised immunity. Mar.
Drugs 18, 254.
Tewari, D., Rawat, P., Singh, P.K., 2019. Adverse drug reactions of anticancer drugs
derived from natural sources. Food Chem. Toxicol. 123, 522–535.
Tsubaki, S., Oono, K., Hiraoka, M., Onda, A., Mitani, T., 2016. Microwave-assisted
hydrothermal extraction of sulfated polysaccharides from Ulva spp. and Monostroma
latissimum. Food Chem. 210, 311–316.
Tziveleka, L.-A., Ioannou, E., Roussis, V., 2019. Ulvan, a bioactive marine sulphated
polysaccharide as a key constituent of hybrid biomaterials: a review. Carbohydr.
Polym. 218, 355–370.
Udayangani, R., Somasiri, G., Wickramasinghe, I., Kim, S.K., 2020. Potential health
benefits of sulfated polysaccharides from marine algae. Encycl. Mar. Biotechnol. 1,
629–635.
Vecchi, V., Barera, S., Bassi, R., Dall’Osto, L., 2020. Potential and challenges of
improving photosynthesis in algae. Plants 9, 67.
Venturuzzi, A.L., Rodriguez, M.C., Conti, G., Leone, M., Caro, M.D.P., Montecchia, J.F.,
Zavallo, D., Asurmendi, S., 2021. Negative modulation of SA signaling components
by the capsid protein of tobacco mosaic virus is required for viral long-distance
movement. Plant J.
Vimala, T., Poonghuzhali, T., 2017. In vitro antimicrobial activity of solvent extracts of
marine brown alga, Hydroclathrus clathratus (C. Agardh) M. Howe from Gulf of
Mannar. J. Appl. Pharm. Sci. 7, 157–162.
Vimala, T., Poonguzhali, T.V., Sakthivel, M., 2021. Potential health benefits of fucoidan:
an update. Phycobiotechnol. Apple Acad. Press 141–185.
Vinayak, V., 2020. Chloroplast gene markers detect diatom DNA in a drowned mice
establishing drowning as a cause of death. Electrophoresis 41, 2144–2148.
Vinayak, V., Gautam, S., 2019. Diatoms in forensics: a molecular approach to diatom
testing in forensic science. Diatoms: Fundam. Appl. 435–470.
Vinayak, V., Gordon, R., Gautam, S., Rai, A., 2014. Discovery of a diatom that oozes oil.
Adv. Sci. Lett. 20, 1256–1267.
46
Journal of Biotechnology 349 (2022) 32–46
Vinayak, V., Manoylov, K.M., Gateau, H., Blanckaert, V., Hérault, J., Pencreac’h, G.,
Marchand, J., Gordon, R., Schoefs, B., 2015. Diatom milking: a review and new
approaches. Mar. Drugs 13, 2629–2665.
Vinayak, V., Khan, M.J., Jha, A.N., Mangesh, H., 2021a. Photosystem I P700 chlorophyll
a apoprotein A1 as PCR marker to identify diatoms and their associated lineage.
J. Eukaryot. Microbiol., e12866
Vinayak, V., Khan, M.J., Varjani, S., Saratale, G.D., Saratale, R.G., Bhatia, S.K., 2021b.
Microbial fuel cells for remediation of environmental pollutants and value addition:
special focus on coupling diatom microbial fuel cells with photocatalytic and
photoelectric fuel cells. J. Biotechnol.
Vo, T.S., Ngo, D.H., Kang, K.H., Jung, W.K., Kim, S.K., 2015. The beneficial properties of
marine polysaccharides in alleviation of allergic responses. Mol. Nutr. Food Res. 59,
129–138.
vonRanke, N., Ribeiro, M., Miceli, L., de Souza, N., Abrahim-Vieira, B., Castro, H.,
Teixeira, V., Rodrigues, C., Souza, A., 2020. Structure-Activity relationship,
molecular docking, and molecular dynamic studies of diterpenes from marine
natural products with Anti-HIV activity. J. Biomol. Struct. Dyn. 1–11.
Varjani, S., Bajaj, A., Purohit, H.J., Kalia, V.C., 2021. Bioremediation and circular
biotechnology. Indian Journal of Microbiology 61 (3), 235–236.
Wang, B., Yang, Z., Gao, D., Wang, F., Liu, M., Chen, G., Ma, L., Yu, X., 2021. Design of
fusion protein for efficient preparation of cyanovirin-n and rapid enrichment of
pseudorabies virus. Biotechnol. Lett. 1–9.
Wang, H.-M.D., Li, X.-C., Lee, D.-J., Chang, J.-S., 2017. Potential biomedical applications
of marine algae. Bioresour. Technol. 244, 1407–1415.
Wang, Y., Xing, M., Cao, Q., Ji, A., Liang, H., Song, S., 2019. Biological activities of
fucoidan and the factors mediating its therapeutic effects: a review of recent studies.
Mar. Drugs 17, 183.
Wan-Loy, C., Siew-Moi, P., 2016. Marine algae as a potential source for anti-obesity
agents. Mar. Drugs 14, 222.
Wells, M.L., Potin, P., Craigie, J.S., Raven, J.A., Merchant, S.S., Helliwell, K.E., Smith, A.
G., Camire, M.E., Brawley, S.H., 2017. Algae as nutritional and functional food
sources: revisiting our understanding. J. Appl. Phycol. 29, 949–982.
Widyaswari, S., Amir, N., 2021 A review: bioactive compounds of macroalgae and their
application as functional beverages. IOP Conference Series: Earth and Environmental
Science. IOP Publishing, p. 012002.
Wu, H.-L., Wang, G.-H., Xiang, W.-Z., Li, T., He, H., 2016. Stability and antioxidant
activity of food-grade phycocyanin isolated from Spirulina platensis. Int. J. Food
Prop. 19, 2349–2362.
Wu, S.-C., 2017. In: Xu, Z. (Ed.), Antioxidant Activity Of Sulfated Seaweeds
Polysaccharides by Novel Assisted Extraction. Solubility of Polysaccharides.
IntechOpen, London, UK, pp. 89–108.
Yadav, G., Sekar, M., Kim, S.-H., Geo, V.E., Bhatia, S.K., Sabir, J.S., Chi, N.T.L.,
Brindhadevi, K., Pugazhendhi, A., 2021. Lipid content, biomass density, fatty acid as
selection markers for evaluating the suitability of four fast growing cyanobacterial
strains for biodiesel production. Bioresour. Technol. 325, 124654.
Yaich, H., Amira, A.B., Abbes, F., Bouaziz, M., Besbes, S., Richel, A., Blecker, C., Attia, H.,
Garna, H., 2017. Effect of extraction procedures on structural, thermal and
antioxidant properties of ulvan from Ulva lactuca collected in Monastir coast. Int. J.
Biol. Macromol. 105, 1430–1439.
Yang, X., Wu, Q., Zhang, J., Huang, J., Chen, L., Wu, S., Zeng, H., Wang, J., Chen, M.,
Wu, H., 2019. Prevalence, bacterial load, and antimicrobial resistance of Salmonella
serovars isolated from retail meat and meat products in China. Front. Microbiol. 10,
2121.
Yasuhara-Bell, J., Lu, Y., 2010. Marine compounds and their antiviral activities. Antivir.
Res. 86, 231–240.
Yu, W., Zhang, M., Wang, B., Xu, R., Pang, T., Liu, J., 2021. Dietary Haematococcus
pluvialis powder supplementation affect carotenoid content, astaxanthin isomer,
antioxidant capacity and immune-related gene expression in Pacific white shrimp,
Litopenaeus vannamei. Aquac. Res. 52, 2403–2414.
Yusof, R., Rothan, H., 2020. Antiviral and virucidal activities of sulphated
polysaccharides against Japanese encephalitis virus. Trop. Biomed. 37, 713–721.
Zerrifi, S.E.A., El Khalloufi, F., Oudra, B., Vasconcelos, V., 2018. Seaweed bioactive
compounds against pathogens and microalgae: potential uses on pharmacology and
harmful algae bloom control. Mar. Drugs 16, 55.
Zhang, C., Liu, P., 2017. The lipid droplet: a conserved cellular organelle. Protein Cell 8,
796–800.
Zhang, C., Chen, X., Wang, J., Tan, L., 2017. Toxic effects of microplastic on marine
microalgae Skeletonema costatum: interactions between microplastic and algae.
Environ. Pollut. 220, 1282–1288.
Zhang, W., Wu, W., Bao, Y., Yan, X., Zhang, F., Linhardt, R.J., Jin, W., Mao, G., 2021.
Comparative study on the mechanisms of anti-lung cancer activities of three sulfated
galactofucans. Food Funct.
Zhang, Z., Wang, F., Wang, X., Liu, X., Hou, Y., Zhang, Q., 2010. Extraction of the
polysaccharides from five algae and their potential antioxidant activity in vitro.
Carbohydr. Polym. 82, 118–121.
Zhao, X., Zhang, J., Zhu, K.Y., 2019. Chito-protein matrices in arthropod exoskeletons
and peritrophic matrices. Extracellular Sugar-Based Biopolymers Matrices. Springer,
pp. 3–56.
Zhao, Z., Bermudez, S.C., Ilyas, A., Muylaert, K., Vankelecom, I.F., 2020. Optimization of
negatively charged polysulfone membranes for concentration and purification of
extracellular polysaccharides from Arthrospira platensis using the response surface
methodology. Sep. Purif. Technol. 252, 117385.