Perkembangan Penelitian

Obat dan Vaksin COVID-19

di Indonesia
Linda Erlina

Departemen Kimia Kedokteran FKUI

Klaster Bioinformatics Core Facilities – IMERI-FKUI
 • Update: COVID19 Global and Indonesia
• Drug discovery and development stages
• Therapeutic options for COVID-19
• Acceleration strategies for SARS-CoV-2 drug
Outlines discovery
• Drug repurposing for COVID-19
• Vaccine Research for COVID-19
 Update: COVID-19 Global and
Indonesia

Confirmed Case Recovery Death

Global
(216 countries) : 8.327.805 8.525.042 449.182 456.973
(19 June 2020) (20 June 2020) (19 June 2020) (20 June 2020)

Indonesia : 43.803 45.029 17.349 17.883 2.373 2.429

(19 June 2020) (20 June 2020) (19 June 2020) (20 June 2020) (19 June 2020) (20 June 2020)

https://www.who.int/emergencies/diseases/novel-coronavirus-2019 Last Update: 20 June 2020

https://covid19.go.id/
 Current Status
for COVID-19
Treatment in
The World

https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub
 Drug Discovery and Development Stages

BPOM BPOM

https://www.compoundchem.com/2016/01/16/drug-discovery/
Genome Research Limited (https://www.yourgenome.org/)
 From basic research to pre-clinical stage
Lead candidate
refinement
Synthesis & isolation Mechanism of action
Combinatorial chemistry Cellular disease models
High throughput Drug affinity &
screening selectivity
Lead Discovery In vitro

In vivo
Target Selection
Medicinal Chemistry Animals models of
Cellular & genetic target disease states
In silico and machine
Genomics learning studies Behavioural studies
Proteomics Structure activities Functional imaging
Bioinformatics Library development Ex vivo studies

https://www.compoundchem.com/2016/01/16/drug-discovery/ Chemical synthesis Toxicity studies

 Bioinformatic is a key to reveal the whole
genome sequence of SARS-CoV-2

Zhou et al. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discovery (2020)6:14
 Therapeutic options for COVID-19

• Molecules binding to the virus

• Molecules or inhibitors that target specific enzymes involved in
viral replication and transcription,
• small-molecule inhibitors targeting helicase, essential proteases,
or other proteins of the virus,
• host cell protease inhibitors, host cell endocytosis inhibitors,
• siRNA, anti-sense RNA and ribozyme,
• neutralizing antibodies, mAbs targeting host receptor or
interfere with S1 RBD, antiviral peptide targeting S2
• natural products

Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020.
6LU7 SARS-CoV-2
Inhibitor
Virus:
1. PLPro (Papain-like proteinase)
2. Spike protein
3. Main protease (3CL Pro)
4. RdRp (RNA-dependent RNA
polymerase)

Host:
1. ACE2
2. EIF4
3. TMPRSS2
4. Dipeptidyl Peptidase 4 (DPP4)

Wu, C.,, et al., 2020. Analysis of therapeutic targets for SARS-

CoV-2 and discovery of potential drugs by computational
methods. Acta Pharmaceutica Sinica B.
Acceleration • Bioinformatic pipeline for design new
vaccine and immunotherapeutic
strategies • Computational approaches to accelerate
SARS-CoV-2 drug discovery
for SARS- big data and machine learning (SVM,
random forest, MLP)
CoV-2 drug In silico modelling (pharmacophore
modelling, molecular docking, virtual
discovery screening, molecular dynamic simulation)
 Inhibitor Design for SARS-CoV-2

Database: Feature Extraction

SuperTarget (Fingerprint, dipeptide Pharmacophore modeling
+ literature descriptor)

Machine Learning
(Random Forest, SVM, MLP) Ligand-Based Structure-Based (3CLPro)

Database:
Testing/screening Database:
HerbalDB Virtual screening HerbalDB
Hit compounds

Linda Erlina, Rafika Indah Paramita, Fadilah, Aryo Tedjo, Wisnu Ananta Kusuma,
Arry Yanuar. 2020. Big data analysis with machine learning and pharmacophore
modelling to find potential Indonesian herbal compounds for SARS-CoV-2
Protein-Ligand Docking
inhibition. Preprints. BMC Medical Informatics and Decision Making.
 Pharmacophore
Features 3CLPro (PDB ID:
6LU7)
 Protein-Ligand Docking

https://www.oist.jp/news-center/photos/illustration-systems-docking-simulation
 Ananas 26

Noviyantih, et al. The Invention of Candidate Compounds From Strychnine Bush, Pineapple and Ginger as The Main Protease Receptor Inhibitor of Covid-19 Virus, 2020 (unpublished)
 No Compound name Binding Energy (ΔG) Sources
(kcal/mol)

1 Cyanidin-3-sophoroside-5-glucoside -9.12 Brassica Oleracea, Ipomoea Batatas, Raphanus Sativus

2 Geniposide -7.04 Gardenia jasminoides

3 Hesperidine -8.31 Psidium guajava

Citrus aurantium

4 Isoforskolin -6.88 Coleus forskohlii

5 Kaempferol 3,4'-di-O-methylether (Ermanin) -7.98 Zingiber aromaticum

6 Majoroside -7.03 Plantago major

7 Myricetin-3-glucoside -8.26 Moringa oleifera

8 Oleoside -6.52 Oleaceae familia (e.g Jasminum sambac)

9 Peonidine 3-(4’-arabinosylglucoside) -8.52 Ipomoea fistulosa

10 Quercetin 3-(2G-rhamnosylrutinoside) -8.56 Clitoria Ternatea

11 Rhamnetin 3-mannosyl-(1-2)-alloside -8.32 Moringa oleifera

Cassia alata

12 Sinigrin -1.24 Brassica nigra

13 Spiraeoside -7.97 Filipendula ulmaria

14 Theviridoside -7.13 Thevetia peruviana

15 Lopinavir -9.62 Antiviral drug (positive control)

Linda Erlina, Rafika Indah Paramita, Fadilah, Aryo Tedjo, Wisnu Ananta Kusuma, Arry Yanuar. 2020. Big data analysis with machine learning and pharmacophore modelling to find potential Indonesian herbal
compounds for SARS-CoV-2 inhibition. Preprints. BMC Medical Informatics and Decision Making.
 Site : Universitas Indonesia
Hospital
Clinical Trial Plan
Evaluation of
Effectiveness using Subjects : 50 patients
Psidium guajava as
Nutrition Supplement
for COVID-19 Patients Method : double blind with 2
groups (without
supplementation and
supplementation)
Research Team
1. Dr. Fadilah, S.Si., M.Si
2. Aryo Tedjo, S.Si., M.Si
3. Rafika Indah Paramita, M.Farm., Apt
4. Dr. Eng. Wisnu Ananta Kusuma, S.T., M.T
5. Prof. Dr. Arry Yanuar, M.Si., Apt
6. Dr. Irandi Putra Pratomo, Ph.D., Sp.P FAPSR
7. Khaerunnisa Anbar Setiadi, M.Si
8. Linda Erlina, M.Farm
 Propolis Sebagai Alternatif Pengobatan COVID-19

Dr. Eng. Muhamad Sahlan, S.Si,

M. Eng (Peneliti dari FTUI)

FTUI Kembangkan Propolis Sebagai Alternatif Pengobatan Corona. 5 Maret 2020. https://www.ui.ac.id/ftui-kembangkan-propolis-sebagai-alternatif-pengobatan-corona/
 Jamu Empon-Empon Penangkal COVID-19

https://www.kompas.com/sains/read/2020/03/28/165324423/curcumin-empon-empon-untuk-penangkal-corona-sudah-sampai-mana-risetnya
 • Human coronaviruses (HCoVs), including
severe acute respiratory syndrome
coronavirus (SARS-CoV) and 2019 novel
coronavirus (2019-nCoV, also known as
SARS-CoV-2), lead global epidemics with
Drug high morbidity and mortality.
• However, there are currently no effective
repurposing drugs targeting 2019-nCoV/SARS-CoV-2.
• Drug repurposing, representing as an
for COVID-19 effective drug discovery strategy from
existing drugs, could shorten the time and
reduce the cost compared to de novo drug
discovery.
 Severe Acute
Respiratory
Syndrome
Coronavirus 2
(SARS-CoV-2)
Viral Lifecycle and
Potential Drug
Targets

James M. Sanders. Pharmacologic

Treatments for Coronavirus Disease 2019
(COVID-19) (Review). JAMA May 12, 2020
Volume 323, Number 18
 Network-based
drug repurposing
for novel
coronavirus 2019-
nCoV/SARS-CoV-2

Zhou et al. Cell Discovery (2020)6:14

 Klorokuin dan Hidroksiklorokuin

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda- https://www.cnbcindonesia.com/tech/20200619150910-37-166649/who-
revokes-emergency-use-authorization-chloroquine-and larang-ri-masih-pakai-hydroxychloroquine-buat-corona
 Allupurinol

Decrease c-reactive protein (CRP) as one of cytokine storm marker

https://www.nature.com/articles/s41577-020-0320-7
 Dexamethason
e
Mechanism of action:
1. Reduce cytokine storm
2. Prevent the massive
inflammation

Notes:
Dexamethasone treatment is only
effective for “critically ill” patients.

https://www.who.int/news-room/detail/16-06-2020-who-welcomes-preliminary-
results-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients
 Potensi Lima Kombinasi Terapi untuk COVID-19
Lopinavir
Azithro- Kombinasi
atau 1
micyne
ritonavir

Hidroksi- Azithro- Kombinasi

klorokuin micyne 4

Lopinavir
Kombinasi
atau doxycyline
2
ritonavir

Hidroksi- Doxycycline
Kombinasi
klorokuin 5

Lopinavir
Chlaritro- Kombinasi
atau mycine 3 Obat corona: Klaim temuan 'kombinasi obat' Covid-19, berapa lama penelitian
ritonavir harus dilakukan sebelum obat dinyatakan aman dan efektif?
https://www.bbc.com/indonesia/indonesia-53066979. (akses 17 Juni 2020)
 COVID-19 Vaccine Research

https://www.spandidos-publications.com/10.3892/ijmm.2020.4596
Sampai saat
ini ada 26
data sekuens
SARS-CoV-2
di Indonesia :

16 sekuens
sudah
lengkap

10 sekuens
masih parsial

https://www.epicov.org
Penelitian vaksin
harus
memperhatikan data
mutasi
SARS-CoV-2

https://www.epicov.org
 • Perkembangan penelitian
mengenai obat dan vaksin global
sangat cepat, sehingga perlu
dilakukan kehati-hatian sebelum
diadopsi untuk terapi pasien
COVID-19 di Indonesia.
Penutup • Perlu dilakukan sekuensing Whole
Genom SARS-CoV-2 Indonesia
lebih banyak untuk mengetahui
pola mutasi, sehingga
pengembangan vaksin dan obat
dilakukan lebih spesifik dan efektif.
 • Linda Erlina, Rafika Indah Paramita, Fadilah, Aryo Tedjo, Wisnu
Ananta Kusuma, Arry Yanuar. 2020. Big data analysis with
machine learning and pharmacophore modelling to find potential
Indonesian herbal compounds for SARS-CoV-2 inhibition.
Preprints. BMC Medical Informatics and Decision Making.
• Noviyantih, et al. The Invention of Candidate Compounds From
Strychnine Bush, Pineapple and Ginger as The Main Protease
Receptor Inhibitor of Covid-19 Virus, 2020 (unpublished)
• Lu H. Drug treatment options for the 2019-new coronavirus (2019-
nCoV). Biosci Trends. 2020.
• Wu, C.,, et al., 2020. Analysis of therapeutic targets for SARS-
CoV-2 and discovery of potential drugs by computational methods.
Acta Pharmaceutica Sinica B.
References • Zhou et al. Network-based drug repurposing for novel coronavirus
2019-nCoV/SARS-CoV-2 Cell Discovery (2020)6:14
• https://www.who.int/emergencies/diseases/novel-
coronavirus-2019/question-and-answers-hub
• https://www.who.int/emergencies/diseases/novel-
coronavirus-2019
• https://covid19.go.id/
• https://www.compoundchem.com/2016/01/16/drug-discovery/
• Genome Research Limited (https://www.yourgenome.org/)
• https://www.compoundchem.com/2016/01/16/drug-discovery/
Thank You