Existing Drugs Targeting SARS-CoV-2 and Coronaviruses

Existing Drugs Targeting SARS-CoV-2 and Coronaviruses

All Tocris products mentioned in this blog post are for biomedical research use only. They are not intended for human or veterinary use.

The coronavirus family, named for their crown-like shape, cause respiratory disorders with symptoms ranging from mild, similar to the common cold, to severe and potentially fatal cases, where the virus infects the lower respiratory tract causing viral pneumonia. Recent outbreaks of coronaviruses include:

  • Severe acute respiratory syndrome (SARS), caused by SARS-CoV, 2002 – 2004
  • Middle East respiratory syndrome (MERS), caused by MERS-CoV, 2012
  • COVID-19 caused by SARS-CoV-2, late 2019 - 2020

As well as respiratory infection, SARS-CoV-2 can also affect the gastrointestinal system, heart, kidneys, liver and central nervous system, causing symptoms associated with these organs.

There are currently no drugs to treat COVID-19. Repurposing of approved therapeutics, and compounds with pre-existing clinical data, provides a rapid route to finding a treatment.

SARS-CoV-2 structure and host cell entry mechanism

SARS-CoV-2 and other coronaviruses are positive-sense, single-stranded RNA viruses. This means that the genetic material that they contain is single-stranded RNA, contained in a nucleocapsid with helical symmetry. All viruses require a host cell to reproduce, and they must bind to a receptor on the extracellular surface of the host cell to facilitate viral entry. SARS-CoV-2 is thought to bind to angiotensin converting enzyme 2 (ACE2), which is a single-pass transmembrane protein highly expressed on lung alveolar cells, and expressed on glandular cells, endothelial cells, and enterocytes in the gastrointestinal system.

The Spike glycoprotein expressed on SARS-CoV-2 binds to ACE2 enabling cell entry. Proteases within the host cell are also essential for host cell invasion, as they cleave and activate the Spike protein. Proteases that cleave the SARS-CoV-2 Spike protein include TMPRSS2 and cathepsin B and L. Once bound to ACE2 on the host cell, SARS-CoV-2 enters the cell by endocytosis of ACE2 and the attached virus into endosomes.

RNA within SARS-CoV-2 is then released into the host cell where it is translated into functional viral proteins by the host cell machinery. These proteins include two overlapping polyproteins named pp1a and pp1ab, as well as RNA-dependent RNA polymerase (RdRP) required for viral RNA replication, and two viral proteases: the main protease, Mpro (also known as 3C-like protease, 3CLpro) and the papain-like protease, PLpro. Cleavage of pp1a and pp1ab by 3CLpro and PLpro releases multiple functional proteins that form the replicase complex required for viral replication.

SARS-CoV-2 mechanism of cell entry

Figure 1: SARS-CoV-2 mechanism of cell entry and viral replication. SARS-CoV-2 cell entry is caused by the binding of the spike S protein to ACE2, facilitated by priming of the S protein by TMPRSS2. The viral is internalized by endocytosis then it is uncoated in the acidic environment of lysosomes. Viral genome in the form of single stranded RNA is released, the replicated and translated into functional viral proteins by the host cell machinery. Viral proteins produced include viral proteases and structural components of the virus. Following reproduction, the viral components are assembled and released via vesicular exocytosis.

Compounds to treat COVID-19

Multiple small molecules that are approved to treat other disorders have shown promise against key proteins involved in SARS-CoV-2 host cell entry and replication.

Camostat (Cat. No. 3193) – Broad spectrum protease inhibitor. Inhibits TMPRSS2 in the host cell and partially prevents entry of SARS-CoV-2 into lung cells in vitro. Full inhibition of viral cell entry is seen when combined with E 64d (Cat. No. 4545), a cathepsin B and L inhibitor.

Chloroquinine (Cat. No. 4109) – Immune modulator and antimalarial. Increases endosomal pH, preventing the acidic conditions required for virus/endosome fusion. Inhibits SARS-CoV-2 infection in vitro.

Hydroxychloroquinine (Cat. No. 5648) - Immune modulator and antimalarial, derivative of Chloroquinine. Increases endosomal pH, preventing the acidic conditions required for virus/endosome fusion. Inhibits SARS-CoV-2 infection in vitro

Ribavirin (Cat. No. 4501) – Antiviral ribonucleoside analog; binds to SARS-CoV-2 RdRP in a molecular docking study. Incorporated in RNA strand, blocking strand elongation and replication.

Ritonavir (Cat. No. 5856) – HIV protease inhibitor; improves outcome of MERS-CoV infection in animal model, in combination with lopinavir.

Tocriscreen PRO COVID-19 Compound Library – 285 bioactive compounds to explore key pharmacological targets related to COVID-19. Multiple formats available and customizable to your requirements. Please complete the compound library inquiry form.


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Elfiky (2020) Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. Epub ahead of print. PMID: 32222463

Gordon et al. (2020) A SARS-CoV-2-human protein-protein interaction map reveals drug targets and potential drug repurposing. BioRxiv. Not yet peer reviewed.

Hoffmann et al. (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically-proven protease inhibitor. Cell. 181, 271. PMID: 32142651

Liu et al. (2020) Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 6, 16. PMID: 32194981

Wang et al. (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30, 269. PMID: 32020029