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SARS-CoV-2 —— The Culprit of Global Pandemic COVID-19

SARS-CoV-2The Battle against Coronavirus has just Begun

SARS-CoV-2 showed highly pathogenic, caused severe or even life-threatening diseases, and still transmitted from person-to-person.
The World Health Organization declared a global pandemic as the coronavirus (SARS-CoV-2) rapidly spreads across the world.
Until now, no drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19.

SARS-CoV-2Promising Antiviral Agents

Favipiravir (T-705)
Selectively and potently inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses[1]. Shows good clinical efficacy in treating COVID-19[2].
Remdesivir (GS-5734)
A nucleotide analog inhibitor of RdRp. Against SARS-CoV, MERS-CoV and Ebola virus[3]. Effectively inhibits
SARS-CoV-2 in vitro[4]. Enters phase III trial.
Chloroquine Phosphate
An antimalarial agent. Inhibits autophagy and toll-like receptors (TLRs)[5]. Effectively inhibits SARS-CoV-2 in vitro[6]. FDA approved.
Hydroxychloroquine sulfate
An antimalarial and anti-inflammatory agent. Inhibits TLR7/9 signaling[7]. Efficiently inhibits SARS-CoV-2 infection in vitro[6]. FDA approved.
Umifenovir hydrochloride
A broad-spectrum antiviral chemical agent. Inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane.
Galidesivir hydrochloride
A viral RdRp inhibitor. Inhibits SARS-CoV-2 by tightly binding to its RdRp.
Forodesine hydrochloride
Highly potent and specific purine nucleoside phosphorylase (PNP) inhibitor. Induces apoptosis in leukemic cells by increasing the dGTP levels.
GS-443902 trisodium
Active triphosphate metabolite of Remdesivir. A potent viral RdRp inhibitor with IC50s of 1.1 µM and 5 µM for RSV RdRp and HCV RdRp, respectively.
Ebselen (SPI-1005)
A potent voltage-dependent calcium channel (VDCC) blocker. Potently inhibits Mpro (IC50=0.67 μM) and COVID-19 virus (EC50=4.67 μM). HIV-1 capsid CTD dimerization inhibitor. Can permeate the blood-brain barrier. Has anti-inflammatory, antioxidant and anticancer activity.

Chloroquine and its Family MembersA New Direction in the Field of Coronavirus Research

  • Subfamily Members
  • Relationship
  • Mechanism of Action
  • Clinical Status and Indication
Chloroquine Subfamily
Chloroquine Representative Drug Autophagy, RNA-dependent
RNA polymerase, TLR
Approved: Malaria, Tumor, Rheumatoid Arthritis,
COVID-19, etc
Preclinical Research: Chikungunya Virus
Didesethyl Chloroquine Major Metabolite of
Autophagy, RNA-dependent
RNA polymerase
Preclinical Research: Malaria, Chikungunya Virus
Hydroxychloroquine Less Toxic Metabolite of
Autophagy, RNA-dependent
RNA polymerase, TLR
Approved: Malaria, Tumor, Rheumatoid Arthritis,
COVID-19, etc
Preclinical Research: Chikungunya Virus
Cletoquine Major Active Metabolite of
Autophagy, RNA-dependent
RNA polymerase
Preclinical Research: Chikungunya Virus,
Ferroquine Subfamily
Ferroquine Chloroquine Analog Autophagy, Ferroptosis Phase II: Malaria
Preclinical Research: Tumor, Virus
Desmethyl Ferroquine Major Metabolite of
Autophagy, RNA-dependent
RNA polymerase
Preclinical Research: Malaria, Virus
Derivative of Ferroquine   Preclinical Research: Malaria, SARS-CoV
Other Subfamily
Primaquine Chloroquine Analog ROS Approved: Malaria, HIV
Mefloquine Chloroquine Analog Heme polymerase Approved: Malaria
Preclinical Research: Osteoporosis
Amodiaquine Chloroquine Analog Heme polymerase Approved: Malaria
Preclinical Research: Ebola Virus
N-Desethyl amodiaquine Major Active Metabolite of
  Preclinical Research: Malaria

Nucleoside & Nucleotide AnaloguesA Major Class of Antiviral Drugs

Nucleosides/nucleotides are endogenous compounds that are related to the regulation and modulation of many physiological processes, such as DNA and RNA synthesis, cell signaling, enzyme regulation and metabolism.

They are synthetic, chemically modified compounds that mimic their physiological counterparts. They exploit cellular metabolism in order to be incorporated into DNA and RNA, inhibiting cellular division and viral replication. Nucleoside/nucleotide analogues represent a major class of anticancer and antiviral drugs.

  • Condition
  • Compound
  • Mechanism
  • Status
Nucleoside & Nucleotide
Nucleoside & Nucleotide
  • Favipiravir
  • Targets RNA-dependent RNA polymerase (RdRp)
  • Approved
  • Tenofovir
  • Targets nucleotide reverse transcriptase
  • Approved
Nucleoside & Nucleotide
  • Linezolid
  • Inhibits bacterial protein synthesis
  • Approved
  • Nitrofurantoin
  • Inhibits bacterial DNA, RNA and protein synthesis
  • Approved
  • Isoniazid
  • Acts on the mycobacterial cell wall
  • Approved

MedChemExpress Anti-COVID-19 Compound Library based on Relevant Proteins :

We conduct Virtual Screening of approved compound library and clinical compound library based on 3CLpro (PDB ID: 6LU7), RdRp, Spike Glycoprotein (PDB ID: 6VSB), nsp15 (PDB ID: 6VWW), PLpro and ACE2 Structure.

SARS-CoV and MERS-CoV structure and replication

SARS-CoV and MERS-CoV structure and replication[12].

SARS-CoV-2 belongs to the Coronavirus genus in the Coronaviridae family and has a positive-sense RNA genome. Coronavirus contain four main structural proteins: spike(S), membrane (M), envelope (E), and nucleocapsid (N) proteins[8].
Attachment of the virion to the cell surface via a receptor constitutes the first step in the coronavirus life cycle[9]. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as a cellular entry receptor[10]. Then, the virus must gain access to the host cell cytosol. This is generally accomplished by TMPRRS2 or another protease. The next step is the translation of the replicase gene from the virion genomic RNA. The replicase gene encodes two large ORFS, rep1a and rep1b, which express two co-terminal polyproteins, pp1a and pp1ab[11]. They are proteolytically cleaved into 16 non structural proteins (nsps), including papain-like protease (PLpro), 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), helicase (Hel) and exonuclease (ExoN)[12].
Viral RNA synthesis follows the translation and assembly of the viral replicase complexes. It involves two stages: genome replication and subgenomic RNA transcription. Subgenomic RNAs serve as mRNAs for the structural and accessory genes which reside downstream of the replicase polyproteins[9] [11]. Following replication and subgenomic RNA synthesis, the viral structural proteins, S, E, and M are translated and inserted into the endoplasmic reticulum (ER). The mature virions are formed. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis[11].

Partial Screening Library Data :

SARS-CoV-2 Compound Information Status
3CLpro Saquinavir An HIV Protease inhibitor. FDA approved
Carfilzomib An irreversible proteasome inhibitor. FDA approved
Nelfinavir An orally bioavailable HIV-1 protease inhibitor (Ki=2 nM) and antiviral agent. FDA approved
S Protein & ACE2 Bimosiamose A nonoligosaccharide pan-selectin inhibitor and has anti-inflammatory effects. Phase 2
RdRp Zanamivir An influenza viral neuraminidase inhibitor. FDA approved
nsp15 Ribavirin An antiviral agent against a broad spectrum of viruses including HCV, HIV,
and RSV.
FDA approved
PLpro Epetraborole
A leucyl-tRNA synthetase (LeuRS) inhibitor. Intended for the infections caused
by Gram-negative bacteria.
Phase 2

Antiviral Natural Products:

Forsythia suspensa Lonicera japonica Thunb Ephedra Semen Armeniacae amarum
Isatis indigotica L Dryopteris crassirhizoma Nakai Houttuynia cordata Pogostemon cablin
Rheum Rhodiola rosea Glycyrrhiza uralensis Menthol


Arenavirus Bacterial CMV Enterovirus
Filovirus Fungal HBV HCV
HCV Protease HIV HIV Protease HSV
Influenza Virus Parasite Reverse Transcriptase RSV
SARS-CoV Virus Protease    


1. Furuta Y, et al. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463.
2. Favipiravir shows good clinical efficacy in treating COVID-19: official.
3. Agostini ML, et al. mBio. 2018 Mar 6;9(2).
4. Wang M, et al. Cell Res. 2020 Mar;30(3):269-271.
5. Mohamed FE, et al. Liver Int. 2015 Mar;35(3):1063-76.
6. Yao X, et al. Clin Infect Dis. 2020 Mar 9. pii: ciaa237.
7. Lamphier M, et al. Mol Pharmacol. 2014 Mar;85(3):429-40.
8. Guo, Y., et al. Mil Med Res. 2020 Mar 13;7(1):11.
9. Graham RL, et al. Virus Res. 2008 Apr;133(1):88-100.
10. Wanbo Tai, et al. Cell Mol Immunol. 2020 Mar 19.
11. Fehr AR, et al. Methods Mol Biol. 2015;1282:1-23.
12. de Wit E, et al. Nat Rev Microbiol. 2016 Aug;14(8):523-34.