Article Figures & Data
Figures
- Fig. 1.
SARS-CoV-2 spike (S) protein binds the cell surface receptor ACE2 on host cells. Viral genome is delivered into the host cytosol by 1) directly fusing with the plasma membrane after being cleaved and activated by the serine protease TMPRSS2 or 2) using the host cell’s endocytic machinery in which the endocytosed virions are subjected to an activation step in the endosome. The viral genome also functions as the messenger RNA, which is translated into proteins, such as 3CLPro, papain-like cysteine protease (PLpro), and RdRp, by host cell machineries. The SARS-CoV-2 genome also encodes the structural proteins (S), envelope (E), membrane (M), and nucleocapsid (N). RdRP is essential for viral replication and therefore is an attractive target for anti–SARS-CoV-2 drugs. Drugs that are currently in clinical trials are shown here in red, along with their targets of viral life cycle or viral-host interactions. Figure created in BioRender.
Tables
Cell line Assay type Strain of SARS-CoV-2 Library screened Reference Caco-2 CPE Unspecified 5632 compounds, including 3488 compounds that have undergone clinical investigationsa B. Ellinger et al., preprint, DOI: https://doi.org/10.21203/rs.3.rs-23951/v/v1 Vero E6 Primary screen: CPE
Follow-up: N protein immuno-fluorescenceHKU-001a in 1’ screen USA-WA1/2020 for follow-up LOPAC 1280 and ReFRAME librarya L. Riva et al., preprint, DOI: https://doi.org/10.1101/2020.04.16.044016 Vero E6 CPE BavPat1 strain Prestwick Chemical Library (1520 approved drugs) F. Touret et al., preprint, DOI: https://doi.org/10.1101/2020.04.03.023846 CPE, cytopathic effect.
↵a Proprietary library.
Compound/treatment Target Phase ClinicalTrials.gov identifier Approved for other clinical treatment Status Camostat mesilate Serine proteases, e.g., TMPRSS2 Phase 1/2 NCT04321096 Acute pancreatitis (Japan) Ongoing Chlorpromazine Clathrin-mediated endocytosis Phase 1/2 NCT04354805 Schizophrenia, manic depression, nausea, anxiety Not yet recruiting Phase 3 NCT04366739 Not yet recruiting Ciclesonide, an inhaled corticosteroid Viral nonstructural protein 15 encoding an endonuclease and host process Phase 2 NCT04330586 Asthma and allergic rhinitis (Schaffner and Skoner, 2009) Not yet recruiting Favipiravir (Avigan) with tocilizumab RdRp Not applicable NCT04310228 Influenza (Japan) Ongoing IL-6 Hydroxychloroquine and chloroquine Antiviral properties unclear Various Multiple Malaria, autoimmune diseases (e.g., lupus, rheumatoid arthritis) Varies Interferon-α1b nasal drops Host immune response to virus Phase 3 NCT04320238 None Ongoing Ivermectin Viral transport into host nucleus Varies Multiple Antiparasitic Ongoing Lopinavir + ritonavir (Kaletra) 3CLpro Phase 4 NCT04252885 HIV Ongoing; preliminary results show no benefit beyond standard care (Baden and Rubin, 2020) Lopinavir-ritonavir + ribavirin and interferon beta-1b 3CLpro, viral polymerase, host immune response to virus Phase 2 NCT04276688 HIV Completed; significant improvement in outcomes (Hung et al., 2020) Nafamostat Serine protease Phase 1 NCT04352400 Pancreatitis (Japan and Germany) Not yet recruiting Niclosamide Viral and host processes Phase 2 and 3 NCT04345419 Anthelminthic drug Not yet recruiting Nitazoxanide Viral and host processes Various Multiple Antiparasitic drug Ongoing Remdesivir RdRp Phase 3 NCT04257656 HIV Terminated NCT04252664 Terminated NCT04292899 Ongoing NCT04280705 Ongoing Tocilizumab or sarilumaub Human mAb that inhibits the IL-6 pathway by binding and blocking the IL-6 receptor Various Multiple Multiple, including chimeric antigen receptor T cell–induced cytokine release syndrome, other autoimmune conditions (Barlow et al., 2020) Ongoing Umifenovir (Arbidol) Viral membrane fusion of influenza a and b Phase 4 NCT04260594 Influenza (Russia and China) Not yet recruiting - TABLE 3
Potential vaccines in clinical trials for COVID-19 as of June 29, 2020
Sources: who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines; clinicaltrials.gov; clinicaltrialsregister.eu.
Vaccine category Vaccine type Vaccine developer Phase Vaccine identifier DNA based DNA plasmid + electroporation Inovio Pharmaceuticals Phase 1 NCT04336410 DNA vaccine, GX-19 Genexine Consortium Phase 1 NCT04445389 Inactivated virus Inactivated Beijing Institute of Biologic Products Phase 1/2 ChiCTR2000032459 Inactivated Wuhan Institute of Biologic Products Phase 1/2 ChiCTR2000031809 Inactivated Sinovac Research & Development Co., Ltd Phase 1/2 NCT04352608 Phase 1/2 NCT04383574 Inactivated Chinese Academy of Medical Sciences Phase 1/2 NCT04412538 Nonreplicating viral vector Adenovirus type 5 CanSino Biologic Inc; preliminary results (Zhu et al., 2020) Phase 1 NCT04313127 Beijing Institute of Biotechnology Phase 2 ChiCTR2000031781 ChAdOx1-S University of Oxford/AstraZeneca Phase 3 Phase 2/3 ISRCTN89951424 Phase 2/3 2020-001228-32 Phase 1/2 NCT04400838 Phase 1/2 2020-001072-15 NCT04324606 Adenoviral Gamaleya Research Institute Phase 1 Phase 1/2 NCT04436471 NCT04437875 Adeno based Chinese Academy of Medical Sciences Phase 2 NCT04341389 NCT04412538 Protein subunit Recombinant SARS-CoV-2 trimeric S protein subunit Clover Biopharmaceuticals Inc./GSK/Dynavax Phase 1 NCT04405908 Recombinant protein (RBD dimer) Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd/The Second Affiliated Hospital of Chongqing Medical University/Beijing Chao Yang Hospital Phase 1 NCT04445194 Full length recombinant SARS CoV-2 glycoproteinnanoparticle vaccine adjuvanted with Matrix M Novavax Phase 1/2 NCT04368988 RNA Messenger RNA in lipid nanoparticle Moderna/NIH/NIAID; related preclinical study (Corbett et al., 2020) Phase 1 Phase 2 NCT04283461 NCT04405076 Messenger RNA in lipid nanoparticle BioNTech/Fosun Pharma/Pfizer Phase 1/2 2020-001038-36 Phase 1 NCT04368728 mRNA Curevac Phase 1 NCT04449276 mRNA People’s Liberation Army (PLA) Academy of Military Sciences/Walvax Biotech Phase 1 ChiCTR2000034112 Self-amplifying RNA in lipid nanoparticle Imperial College London Phase 1 ISRCTN17072692 GSK, GlaxoSmithKline; NIAID, National Institute of Allergy and Infectious Diseases; NIH, National Institutes of Health.
In this issue
SARS-CoV-2 Drug Discovery
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- Article
- Abstract
- Introduction
- Overview of SARS-CoV-2 Genome and Protein Constituents
- Viral Entry Through the Binding of SARS-CoV-2 Spike Proteins to Angiotensin Converting Enzyme 2 Receptor
- SARS-CoV-2 Has Multiple Viral Entry Mechanisms
- Drug Development Strategies
- SARS-CoV-2 Viral Entry Inhibitors
- Viral Replication Inhibitors
- Host Cell and Viral Targets for Antiviral Drug Development
- Prophylactic Treatment of SARS-CoV-2 Infection
- Other Treatments in Clinical Trials for COVID-19
- Vaccines for SARS-CoV-2
- Perspectives and Conclusion
- Authorship Contributions
- Footnotes
- Abbreviations
- References
- Figures & Data
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