Professional Documents
Culture Documents
SSRN Id3748111
SSRN Id3748111
SSRN Id3748111
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Martin L. Nelwan, PhD
Nelwan Institution for Human Resource Development
Department of Animal Science – Other
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Jl. A. Yani No. 24, Palu 94111, INDONESIA
E-mail: mlnelwan2@gmail.com
Abstract
Objectives: In this study, the author reports the progress in a study of COVID-19 focused on
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SARS-CoV-2, diagnosis of COVID-19, prevention and treatment of COVID-19 as objectives of
this study.
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Study design: Prevention and treatment of COVID-19 via diagnosis, vaccines, Curcuma longa
open access, non-commercial open access, and in English. Other relevant publications were also
included.
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Results: SARS-CoV-2 causes COVID-19. This disease has spread all over the world. Diagnosis
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tools of COVID-19 can include such as nanopore sequencing and real time quantitative (qRT-
PCR). Vaccines can include such as Moderna and Pfizer products. Current promising drugs of
COVID-19 are Curcuma longa (turmeric) and remdesivir. Curcuma longa alone may prevent
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lopinavir/ritonavir. For treatment, Curcuma longa can be taken along with remdesivir or other
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
Conclusions: COVID-19 is caused by SARS-CoV-2. To detect this disease, RT-PCR, for
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instance, can be used. Vaccines are such as Pfizer product. Drugs of COVID-19 include
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Keywords: COVID-19, hydroxychloquine, remdesivir, turmeric, SARS-CoV-2, vaccines
Introduction
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causes coronovirus disease 2019 (COVID-19). China detected SARS-CoV-2 in December 2019
in Wuhan; China.1 This disease has infected as many as 65,870,030 million people and caused
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1,523,583 million people deaths within a year.2
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Several diagnosis tools are available for detecting SARS-CoV-2. These include reverse-
antigen detecting tests may facilitate earlier diagnosis and required action.4
based, and nucleic acid approaches.6 The US Food and Drug Administration (FDA) has
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approved for emergency use of Moderna and Pfizer-BioNTech vaccines in the United State.7,8
The WHO has approved Pfizer BioNTech vaccine for emergency use. Plant extracts, such as
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Curcuma longa (turmeric), can help protect people from COVID-19.9 In Indonesia, National
Food and Drug Agency has approved vaccines of Moderna, Pfizer BioNTECH, and Sinovac for
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
Drugs of COVID-19 are also under development. These include such as remdesivir,
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chloroquine/hydroxychloroquine, dexamethasone, azithromicyn, and doxycycline.10,11
Remdesivir has finished for clinical trial. It reduces clinical recovery time.12
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In this study, the author reports the progress in a study of COVID-19 that focused on
SARS-CoV-2, diagnosis of COVI-19, Curcuma longa for protection and treatment of COVID-
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Methods
The author searched Google, ScienceDirect, and the PubMed Database at National Center
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for Biotechnology (NCBI) for articles on COVID-19. Articles included unrestricted free open
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access, free open access articles for non-commercial, articles with permissions if required, and in
English. Publication dates of these articles were unrestricted. Keywords used for searches of
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articles included such as genetic of SARS-Cov-2, transmission, Curcuma longa and COVID-19,
betacoronavirus.6,13 Several types of coronaviruses can infect humans. These include alpha
coronaviruses such as human coronavirus 229E and human coronavirus NL63, and
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The SARS-CoV-2 genome sequence shares about 79-82% sequence identity with SARS-
CoV and shares about 50% identity with MERS-CoV.6,1316 The spike gene of SARS-CoV-2 is
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extremely variable from SARS-CoV. It shares less than 75% nucleotide identity. Viral replicas
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proteins form the RNA-dependent RNA polymerase, nsp12 derived from ORF1b. Then, replicate
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components reorganize the endoplasmic reticulum (ER) into double-membrane vehicles
(DMVs). Double-membrane vehicles assist viral replication of genomic and sub genomic RNAs
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(sgRNA). Sub genomic RNAs are translated into accessory and viral structural proteins. Either
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SARS-CoV-2, and NL63. However, NL63 receptor-binding domain (RBD) has a construction
radically dissimilar from those of SARS-CoV and CoV-2. The receptor-binding domain of
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SARS-CoV-2 binds extra powerfully to the ACE2 receptor than that of SARS-CoV. Strong
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binding of SARS-CoV-2 to ACE2 receptor is a vital cause for the higher infection rate in SARS-
and respiratory droplets. Reproductive number (RO) of SARS-CoV-2 is about 2.3 to 5.7, while
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SARS-CoV is about 3. This virus replication results in mild viremia. The maximum propagation
distance of aerosols containing SARS-CoV-2 virion is 4 meters from patients with COVID-19.
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Severe acute respiratory syndrome CoV-2 aerosols remained infectious in the tissue culture
experiments, and the infectivity decreased slightly during a three-hour observation period. The
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SARS_CoV-2 also exists in stool samples. The fecal oral routes of SARS-CoV-2 occur only on
The clinical characteristic of COVID-19 can be very heterogeneous with a wide spectrum
of severity, including diseases that result in death. Asymptomatic individuals can transmit
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SARS-CoV-2 infection. Individuals more than 65 years old, individuals of all ages whose serious
This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
underlying medical conditions, and those who are immunocompromised, have higher risk of
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serious illness and troubles of COVID-19. Death is higher in male patients who are older than
female patients.6
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The highly pathogenic SARS-CoV-2 infection causes severe ‘flu’ like symptoms. It can
progress to acute respiratory distress (ARDS), pneumonia, renal failure, and death.13 The most
common symptoms are fever, cough, and dyspnea,13,18,19 which include 83%, 82% and 31% of
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patients with COVID-19, respectively. The incubation period is about five to six days. Children
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The adult group with SARS-Cov-2 infection consists of asymptomatic/pre-symptomatic,
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mild, moderate, severe, and critical. Asymptomatic/pre-symptomatic has no symptoms consistent
with COVID-19. Mild patients have a variety of signs and symptoms. These can include cough,
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diarrhea, fever, headache, loss of taste and smell, malaise, muscle pain, nausea, sore throat, and
vomiting. Moderate patients show evidence of lower respiratory during clinical assessment or
imaging and have saturation of oxygen (SpO2) ≥ 94% in room air at sea level. Severe patients
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have SpO2 ≤ 94% on room air at sea level. Finally, critical illness has respiratory failure, septic
shock, and/or multiple organ dysfunctions. Patients with co-morbidities are at higher risk of
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developing severe COVID-19. Co-morbidity can include patients 65 years or older, have
cardiovascular disease, chronic lung disease, diabetes, cancer, obesity, or chronic kidney disease,
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and are receiving immunosuppressive therapy. These patients should be closely monitored until
Diagnosis
Rapid and initial diagnosis of COVID-19 is the focus of treatment and control. Molecular
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tests are the basis for confirmation of COVID-19. Serological tests for SARS-CoV-2, which are
This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
available, play a key role in recognizing the epidemiology of the virus and in recognizing
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populations at higher risk for infection. Point-of-care tests are accurate, low cost and non-
specific device requirements, portable, and rapid. These tests provide terrific help for disease
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diagnosis and detection.17
Sequencing
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Compared with other sequencing platforms, the nanopore-sequencing technology has a
longer read length and performs direct RNA sequencing. The instrument in nanopore sequencing
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is compact. It has certain advantages in pathogen detection. For example, MinION nanopore
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sequencing could detect a variety respiratory viruses including SARS-CoV-2 within six to ten
hours (Table 1). However, the current sequencing platforms are difficult to achieve inexpensive
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and fast detection. It has not been extensively used in the prevention and control of this
epidemic.19
Among the various partitioning methods, such as microwell plates and oil emulsion,
ddPCR is the method most extensively used with commercially available systems. Droplet
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digital PCR has a higher sensitivity than conventional PCR5 or qRT-PCR.17. That makes it
possible for detecting very low viral loads. For example, when pharyngeal swab samples from
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patients with COVID-19 were compared, ddPCR detected viral DNA in 64.2% of RT-PCR
negative samples.5 In addition, ddPCR is more expensive than qPCR for each test performed
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using dedicated instruments and consumables.14 This instrument identifies low level of SARS-
CoV-2 RNA. It has all the keys characteristics that would let its use to enhance and quicken
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
Real-time quantification RT-PCR
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World Health Organization recommends a real-time quantitative PCR (qRT-PCR)
protocols to detect SARS-CoV-2 for the confirmation test. The target genes for detecting SARS-
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CoV-2 are dissimilar in China (ORF1ab and N genes), France (RdRP1 and RdRP2 targets),
Germany (RdRP, E and N genes), Japan (pancorona and multiple targets, spike protein), United
States (N1, N2, N3 genes), and Thailand (ORF1b, N genes). The Centers for Disease Control and
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Prevention (CDC) established a RT-PCR panel for specific detection SARS-CoV-2 and universal
detection SARS-like beta-CoVs. Three sets of primers were used for detecting the N gene. One
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set of primers/probes was universally for detecting all beta-CoVs. The other two were specific
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for detecting SARS-CoV-2. All three targets must be positive for confirmation of COVID-19.
Charite, Germany developed two nucleic acid tests for detecting RdRP and E genes of SARS-
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CoV-2, SARS-CoV, and bat-like beta-CoVs. Both tests, which are positive, could enter the next
step of the test; these are the SARS-CoV-2 specific RT-PCR test and RdRP gene.17
new way to amplify analytical signal with precision down to single-nucleotide variants.
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Generally, these assays use the enzyme Cas12a (CRISPR-associated protein 12a) or Cas13a
(CRIPRS-associated protein 13a). This exploits the collateral cleavage of single-stranded DNA
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(Cas12a) or RNA (Cas13a) by these nucleases. In one method, termed SHERLOCK (specific
high-sensitivity enzyme reporter unlocking), target RNA is first amplified via reverse
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transcribed to the target DNA. CRISPR RNA (crRNA)-Cas13a complex then binds and cleaves
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the target RNA. The complex to provide a fluorescent signal also cleaves non-target RNA probes
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conjugated with a fluorescent dye (F) and quencher (Q) pair. Likewise, the DETECTR (DNA
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endonuclease-targeted CRISPR trans reporter) method uses the crRNA-Css12a complex to
recognize amplified DNA targets. Binding of the crRNA-Cas12a complex to the target DNA
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induces indiscriminate cleavage of the non-target FO-DNA reporter.5
The SHERLOCK technology based on Cas13 and RPA amplification was used for the
detection of SARS-CoV-2.5,17,21 This method designed a nucleic acid test strip specifically
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targeting the spike gene and ORFlab gene of SARS-CoV-2. It could achieve the detection of
SARS-Cov-2 within 1 hour, and the sensitivity was 10 to 100 copies /μL. Except, a strategy
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based on test strips that coupled Cas12 with RT-LAMP to establish a visual detection method for
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SARS-CoV-2 has been reported recently. As low as 10 copies/μL of extract RNA could be
rapid, and simple. This tool is inexpensive in resource poor setting. It is easy to use and portable
for the diagnosis of COVID-19. The CRISPR/Cas technology as DETECTR and AIOD-CRISPR
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can be of great help for large-scale screening of affected populations. These techniques can assist
in routine surveillance and limit the spread of the virus in the community.21
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sensitivity and throughput. It typically uses a multi-well plate coated with viral proteins. The
analytical sensitivity is down to picomolar (pM) ranges, and the typical assay time is two to five
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hours.5
Prevention
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
Three ways are important for preventing COVID-19 (Figure 1). These include use of
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vaccines and plant extracts, Curcuma longa. The other one, which is important for preventing
this disease, includes cover mouth and nose in public with a mask, keep a distance from others,
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and wash hand often.
Vaccines
Vaccines have important a role for preventing COVID-19. The immune response to
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SARS-CoV-2 has not been completely typified. Under such conditions, predictable
computational algorithms may confirm as beneficial tools for detection of immunogenic T-cell
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and B-cell epitopes that can quicken the rational design of SARS-CoV-2 vaccine formulations.
molecules 6 er
However, computer-based algorithms fail to recognize up to 20% of peptides presented by HLA
In addition, current vaccines have little safety data and the efficacy in preventing
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severe disease are unclear. Peer-reviewed publication should resolve these issues.20
before one is proven safe and effective. Several standard platforms, such as inactivated vaccines,
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live-attenuated vaccines, and protein subunit vaccines, are being pursued. Several novel
approaches are being investigated. These include DNA-based and RNA-based approaches,
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replicating, and non-replicating vector approaches. 13 Several vaccine candidates have completed
phase 3 trials.6 These include such as Moderna Inc (Biomedical Advanced Research and
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Development), Pfizer Inc (BioNTech SE), and Sinovac Research and Development (Table 2).1,6
Curcuma longa
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phytochemicals of Curcuma longa L.24 Curcuma longa L. belongs to the family Zingiberacea
This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
with common name of turmeric. It is spice both for vegetarian and non-vegetarian. It also has
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digestive properties.25 Curcuma longa is a yellow chemical compound especially on the root of
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anticancer,26,28,29 and antiprozoa,27 (Table 3). Curcumin is abundant in Asian countries. It has
been used worldwide. These include China, India, Indonesia, Japan, Korea, Malaysia, Pakistan,
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Curcumin is available in several forms. These include capsules, cosmetics, energy drinks,
ointments, soaps, and tablets. The United States FDA has approved curcuminoids as “Generally
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Recognized As Safe” (GRAS), and good tolerability and safety profiles have been shown by
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clinical trials. It is even at doses between 4,000 and 8,000 milligrams per day and at doses up to
Rajagopal et al.9 concluded that from the docking study, the chemical constituents of
Curcuma longa demonstrated better arrangement at a dynamic site. The in silico structuring
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strategy embraced in their investigation helped for recognizing some lead molecules and
furthermore may somewhat clarify their useful impact for further determinations like in vitro and
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in vivo assessments.9 Consuming turmeric regularly may be a useful remedy for preventing the
COVID-19.9,36
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Dietary administration of curcumin with dose of 150 milligrams per kilogram per day
decreased the protein level of AT1 receptor and enhanced the expression of AT2 receptor/ACE2.
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It also resulted in the attenuation of myocardial fibrosis in a rat model of angiotensin II infusion.
An oral dose of curcumin up to 8,000 milligrams per day was safe, acceptable and effective in
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humans. A dose of 500 milligrams, that was taken two times a day during 30 days, is safe37 “A
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
case study” in my institution in June 2019 succeeded to treat gastritis (stomach inflammation)
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using curcumin. It was own experience. An oral dose of curcumin up to 20 grams (about as big
as a thumb), that was taken two times a day during five days (or up to a week) treated the
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disease. Blood type of the patient, who was a 61-year-old man, was type O. Blood pressure was
110/70 mmHg. He was in chronic gastritis. To treat this disease, he took turmeric mixed with
water. To prepare drug for this disease, he cleaned, peeled the curcumin, and mashed it. Then, he
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added about 300 milliliters water (1 glass) and bring to a boil until about 250 milliliters, filtered,
and drunk it. Until now, the patient continued to drink this twice a week (one glass at a time) on
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a regular basis. This dose can also be used two times a week for preventing covid-19. If infected
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with COVID-19, patients can take it two times each day for at least three days. However, this
finding still needs further investigations. Curcuma longa is anti-hypertension; but it can cause
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blood pressure to drop. In addition, Curcuma longa is anti-degenerative on eyes and anti-dengue
(Table 3).
People, who have taken Curcuma longa twice a week for health need or as spices for
food preparation, can also be vaccinated with emergency vaccine(s) for COVID-19. It can help
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protecting healthy people from COVID-19. If infected, patients can take Curcuma longa two
times a day for at least three days for treating the disease. People, who have not yet taken
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Curcuma longa for daily needs, can take it two times a day for at least three days, and then take
it once a day two times a week. These findings still need further evaluations.
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Turmeric in combination with vaccines such as Pfizer BioNTECH and Sinovac can
improve immunity against SARS-CoV-2. For example, in Indonesia efficacy of Sinovac vaccine
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is about 63.5%. It suggests that consuming turmeric regularly can help improve immunity
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against COVID-19.
Treatment
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Use of drug(s) can help treatment of COVID-19 (Figure 1). Drug(s) can include such as
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be a candidate compound for treating SARS-CoV-2. It can repair damage in lungs32 and can
prevent the development of hypertension.31. Curcuma longa can protect various organs (Table
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3).
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The United States FDA approves remdesivir for treatment of COVID-19. In patients with
severe COVID-19, remdesivir reduced the time to clinical recovery. It significantly reduced the
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time to recovery compared to placebo. Ten days versus 15 days was the median time.12
Curcumin alone may treat COVID-19. It can also be used in combination with other
drugs or candidate drugs. For example, it can be used in combination with remdesivir.
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Combination of these both drugs can accelerate the cure of COVID-19. However, this hypothesis
needs further investigations. In case of schistosomiasis, Kura et al.40 suggested that prevention
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(vaccination) in combination with mass drug administration (MDA) using praziquantel can
Conclusions
important role. Diagnosis techniques can include RT-PCR and SHERLOCK. Drugs for this
disease could be Curcuma longa and/or remdesivir. Both can help eliminate COVID-19. For use
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of Curcuma longa in combination with other drugs, it needs future investigations. Curcuma
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
longa is safe and effective. Many countries have used Curcuma longa for daily needs. These
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countries include such as China, India, Indonesia, and the United States. Other drugs may be
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used in combination with Curcuma longa for protecting from COVID-19.
Funding
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Acknowledgement
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Conflict of interest
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I hereby declare that I have no conflicts of interests regarding the content of this article.
References
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Figures
Figure 1. Schematic prevention and treatment of COVID-19 using Curcuma longa, drugs such
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Figure
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Healthy people
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infected people
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Prevention: infected people
Turmeric or People with
Vaccine(s) COVID-19
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er Treatment:
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Turmeric and/or
Remdesivir,
Chloroquine or
Hydroxychloroquine,
Litonavir/ritonavir
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Healthy people
Dead people, if any
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Table
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Table 1. Important diagnosis tools of COVID-19
Tools time references
Kilic et al.5
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DETECTR 30 minutes
ddPCR 60 minutes Li et al.14
Nan et al.16
Kilic et al.5
ELISA 2 to 5 hours Kilic et al.5
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MinION 6 to 10 hours Nan et al.16
sequencing
RDT < 15 minutes Kilic et al.5
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RT-LAMP 15 to 60 minutes Kilic et al.5
El-Azisi and
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Li et al.14
Nan et al.16
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RT-NEAR < 15 minutes Kilic et al.5
RT-RPA 30 minutes Kilic et al.5
RT-qPCR 2 to 4 hours Kilic et al.5
STOP < 70 minutes Kilic et al.5
ot
Kumar et al.18
DETECTR = DNA endonuclease-targeted CRISPR
tn
20
This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
Table
ed
Table 2. Vaccine candidates of COVID-19
NCT number manufacturer references
NCT04324606 University of Oxford Poland et al.6
iew
NCT04336410 Inovio Samrat et al.1
NCT04447781 Pharmaceuticals,
International vaccine
Institute
Samrat et al.1
ev
NCT04334980 Symvivo Cororation
NCT4352608 Sinovac Research Poland et al.6
and Development
Co, Ltd
r
NCT04368728 BioNTech SE Poland et al.6
Pfizer Inc
NCT04400838
NCT04405076
NCT04437875
Moderna Inc
er
University of Oxford
Gamaleya Research
Poland et al.6
Poland et al.6
Poland et al.6
pe
Institute of
Epidemiology
NCT04445389 Genexine Consortium Samrat et al.1
ot
tn
rin
ep
Pr
21
This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
Table
ed
Table 3. Effects of Curcuma longa
Effects references
AntiAlzheimer Valizadeh et al.23
iew
Rajagopal et al.9
Antiaging Rajagopal et al.9
Antibacterial Marbawati and
Umiyati24
ev
Moghadamtousi et al.21
Gupta et al.22
Anticancer Marbawati and
Umiyati24
r
Kali et al.25
Anticoagulants
Antidengue
er
Marbawati and
Umiyati24
Marbawati and
pe
Umiyati24
Antidiabetic Marbawati and
Umiyati24
Rajagopal et al.9
Shamunagarajan et al.28
ot
AntiEbola,
hepatitis, HIV,
HSV, IAV
tn
(influenza)
Antihypertensi Yao et al.29
Aniinflammatory Rajagopal et al.9
Antiprotozoa Marbawati and
rin
Umiyati24
Antischistosomiasis Morais et al.30
Antivirus Marbawati and
ep
Umiyati24
Moghadamtousi et al.21
Cardiac repair Valizadeh et al.23
Wang et al.31
Pr
22
This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
Hepatoprotective Kali et al.25
ed
On degenerative Hewlings and Kalman27
eye condition,
kidney, pain
iew
On lung injury Huang et al.32
Potential therapy Zhu et al.34
for asthma
r ev
er
pe
ot
tn
rin
ep
Pr
23
This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111