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Coronavirus Information

Last updated: 31st March 2020

Given the novelty of SARS-CoV-2 infection (COVID-19), and the lack of proven therapies, a wide variety of strategies are being employed to combat this worldwide epidemic. Many of these emerging strategies rely on repurposing existing drugs, and others are completely new, but all rely on existing scientific evidence of mechanistic approaches that are effective against either similar viral infections or the serious symptoms that are caused by COVID-19.

  • The effects of existing antiviral medications are being evaluated
  • The inflammatory aspects of the disease are being targeted using existing medications including glucocorticoids, COX inhibitors, immunosuppressants and immunomodulators
  • Strategies to block engagement of the virus with its host receptor (ACE2), or inhibition of spike protein activation are being explored
  • Novel inhibitors of the main CoV protease are being developed
  • Mucolytic drugs and drugs to counter pulmonary edema are in clinical trials

All of these tactics are intended to mitigate against COVID-19 and provide a window during which vaccine development can progress (with the caveat that the search for vaccines to prevent infection by existing circulating coronaviruses has been notoriously unsuccessful). The tables provide information gathered from various sources, and aim to cover as many of the pharmacological strategies being considered as we could find. Our ligands (therapeutics) table excludes traditional natural product-based medicines, blood-derived products (e.g. serum from recovered patients and stem cells), investigational vaccines, antibacterials for secondary infections and supportive treatments (oxygen therapy).

The information included here should not be construed as endorsement by the University of Edinburgh, IUPHAR, BPS or the individuals connected with the Guide to Pharmacology database and website. This is a rapidly moving situation, so we make no claim that these are exhaustive lists, but we have tried to provide as accurate information as is available. Our pages for the ligands (therapeutics) and molecular targets in these tables which are in the Guide to Pharmacology have been updated to include literature references and/or links to additional materials. We continue to curate COVID19-related data into our development database, therefore the links in the tables may use alternative public links until the next database release.

Cite this page

If the information on this page is curated by the GtoPdb curation team at the University of Edinburgh. If the information is useful to you, please cite it using the following format:
Faccenda E, Armstrong JF, Davenport AP, Harding SD, Pawson AJ, Southan C & Davies JA. ([date retrieved]). Coronavirus Information. IUPHAR/BPS Guide to Pharmacology. Retrieved from https://www.guidetopharmacology.org/coronavius.jsp

This work is supported by the International Union of Basic and Clinical Pharmacology (IUPHAR) & the British Pharmacological Society (BPS).
To cite the IUPHAR/BPS Guide to Pharmacology more generally please refer to our citation page.

Targets

Target Target ID Comments
ACE2 1614 Anchoring or binding site on host cells that is exploited by some betacoronaviruses for viral entry. Engaged by SARS-CoV-2 spike protein as the first step towards infection of host cells.
TMPRSS2 2421 Involved in the activation of viral glycoproteins/viral entry across a range of viruses, including SARS-CoV-2. SARS-CoV-2 entry is partially blocked in vitro by the protease inhibitor camostat.
SARS-CoV-2 main protease, (MPro; 3C-like proteinase; nsp5) n/a Inhibitors of this viral protease have the potential to block cleavage of nascent viral proteins as they are synthesised in host cells.
CD147 (basigin, HGNC:1116) n/a SARS-CoV-2 may utilise CD147 as an additional entry receptor to infect host cells. The anti-CD147 mAb, meplazumab, can block the interaction between CD147 and SARS-CoV-2 spike protein (bioRxiv preprint article, Wang et al. (2020) https://doi.org/10.1101/2020.03.14.988345). Already under clinical evaluation in NCT04275245.

Ligands

Ligand (Therapeutic) Ligand ID Comments
ACE2 ligands n/a ACE2 ligands that block the site of viral spike protein interaction could offer anti-SARS-CoV-2 infection potential.
anakinra 6972 An approved IL-1 pathway blocking peptide, that has anti-inflammatory action.
ASC09F n/a A combination drug containing ASC09 (a viral protease inhibitor) + ritonavir is an example of an existing HIV therapy being repurposed for COVID-19.
baricitinib 7792 Approved JAK1/2 inhibitor. AI predicts antiviral activity via inhibition of AAK1 which is an important regulator of clathrin-mediated endocytosis, so has potential to inhibit viral entry into host cells in addition to its potent anti-inflammatory efficacy.
bevacizumab 6771 Approved anti-VEGFA mAb. Phase 2/3 NCT04275414 aims to determine if suppression of vascular permeability will reduce pulmonary edema in patients with severe/critical COVID-19.
brincidofovir n/a Small-molecule nucleoside analogue antiviral drug that was developed to treat cytomegalovirus, adenovirus, smallpox, and ebolavirus infections. Potential against SARS-CoV-2 infection could be evaluated.
camostat 6432 Serine protease inhibitor with activity against the host TMPRSS2 protease that is exploited by SARS-CoV-2 to mediate viral entry.
camrelizumab 9758 An anti-PD-1 checkpoint inhibitor approved in China as an immuno-oncology biologic. Being compared to thymosin for the prevention of sepsis in COVID-19 patients.
ciclesonide 7469 Ciclesonide (an approved corticosteroid used to treat respiratory inflammation) can inhibit SARS-CoV-2 replication via inhibition of viral nsp15 (bioRxiv preprint article Matsuyama et al. (2020) https://doi.org/10.1101/2020.03.11.987016).
compound 11r 10706 This is a compound that inhibits the SARS-CoV main protease (Mpro), and has potential to inhibit the SARS-CoV-2 Mpro, structural similarities between the 2 enzymes permitting. X-ray structure of 11r bound to SARS-CoV Mpro is deposited with the RSCB Protein Databank (ID 5N5O).
compound 13b 10720 A more drug-like derivative of 11r (10706) that inhibits the SARS-CoV-2 main protease (Mpro) PMID: 32198291. Exhibits potential for direct delivery to the lungs via inhalation route.
darunavir + cobicistat n/a; 7535 Antiretroviral, protease inhibitor. Cobicistat increases its bioavailability and half life. Phase 3 NCT04252274 for COVID-19
eculizumab 6884 Approved mAb that binds complement factor C5 and blocks membrane attack complex formation.
emapalumab 9295 An approved anti-IFNγ mAb, which could target elevated cytokine production during COVID-19 infection.
emtricitabine + tenofovir n/a NRTI/NtRTI anti-HIV combination that could be repurposed for COVID-19.
enoxaparin 6811 An approved anti-clotting agent. Given evidence of heparin as a potential attachment factor for the coronavirus, a trial to determine the efficacy of early treatment with enoxaparin in COVID-19 patients has been initiated in Italy (March 2020).
favipiravir n/a Small-molecule nucleoside analogue antiviral drug with broad spectrum activity against RNA viruses. A generic version was authorised for marketing by the Chinese National Medical Products Administration in Feb 2020, and can be used for prevention and treatment of COVID-19. Two clinical studies are registered on ClinicalTrials.gov.
fingolimod 2407 An approved S1P1 receptor inhibitor that has immunomodulatory/immunosuppresant actions. This could be applied to the management of the inflammatory aspects of COVID-19. Clinical efficacy will be evaluated in Phase 2 study NCT04280588.
galidesivir n/a Viral RNA-dependent RNA polymerase inhibitor that was originally developed for HCV, EBV, Zika and Marburg virus infections, but also examined for activity against infection by other RNA viruses. Coverage expanded in 2020 to include infections by SARS-CoV-2.
GLS-5300 n/a A Phase 1 MERS vaccine.
hydroxychloroquine 7198 An existing antimalarial drug, with in vitro activity against SARS-CoV (PMID: 16640347), that is being repositioned to treat COVID-19. Preliminary evidence from a small cohort of COVID-19 patients suggests that a combination of hydroxychloroquine + the antibiotic azithromycin significantly reduces detectable viral RNA (compared to hydroxychloroquine alone or placebo; In press 17 March 2020 IJAA DOI : 10.1016/j.ijantimicag.2020.105949). However, extreme caution must be taken when considering using hydroxychloroquine as it has severe cardiac adverse effects, and in addition its distribution to lung tissue is unknown.
I-432 10733 An in vitro tool compound; inhibitor of serine protease TMPRSS2.
meplazumab n/a An anti-CD147 (basigin, BSG) mAb. SARS-CoV-2 may utilise CD147 as an additional entry receptor to infect host cells. Meplazumab can block the interaction between CD147 and SARS-CoV-2 spike protein (bioRxiv preprint article, Wang et al. (2020) https://doi.org/10.1101/2020.03.14.988345). Already under clinical evaluation in NCT04275245.
mucolytic drugs 10692 Ambroxol is an approved mucolytic which has the potential to combat pulmonary congestion in numerous lung conditions.
otamixaban 10732 A direct serine protease factor Xa inhibitor, and failed anticoagulant candidate drug; predicted binding energy when virtually docked with TMPRSS2; associated with bleeding-related adverse effects in clinical study.
PRD_002214 10716 PRD_002214 is a viral main protease inhibitor. It has been crystalised in complex with the SARS-CoV-2 Mpro (RCSB Protein Databank ID 6LU7).
recombinant ACE2 protein (rhACE2) n/a NCT04287686 aims to determine if rhACE2 can act as a decoy for SARS-CoV-2 viruses via engagement of the virus's external spike protein.
recombinant coronavirus S (spike) protein n/a Recombinant spike protein would be predicted to occupy the ACE2 binding site and out-compete S protein on live virus particles to reduce viral infection of host cells. Although note that phase 1 clinical trial NCT01376765 that was looking at SARS-CoV S protein was withdrawn.
recombinant human Type I interferons n/a For example IFNalpha2a (Roferon A), IFNalpha2a (Pegasys) and others, which are already used as antiviral therapies could be applied to COVID-19. IFNs are being evaluated either alone or in various combinations with lopinavir/ritonavir and ribavirin
REGN3051 and REGN3048 n/a A mixture of monoclonal antibodies that target the spike protein of MERS-CoV. Contingent upon similarities within the antigenic sites these may have potential to bind SARS-CoV-2. Progressed as Phase 1 anti-coronavirus clinical lead; NCT03301090 has been completed.
relacatib 7862 Developed as a cathepsin K inhibitor but has activity against cathepsin L that may provide potential to block SARS-Cov-2 entry into host cells.
remdesivir 10715 Nucleotide analogue antiviral with broad-spectrum activity against RNA viruses. Used on compassionate grounds to treat the first SARS-CoV-2 +ve patient in the US. Phase 3 trial NCT04292899 to be carried out in patients with severe COVID-19 is in preparation.
remdesivir + chloroquine 10715; 5535 Effectively inhibits a clinical isolate of SARS-CoV-2 in vitro PMID: 32020029
ribavirin + ritonavir 6842; 8804 Anti-HIV combination that could be repurposed for COVID-19.
ritonavir + lopinavir 8804; n/a NCT04295551. Update: No significant benefit from ritonavir + lopinavir treatment (compared to standard therapy) was observed in patients with severe COVID-19 (results reported for Chinese trial ChiCTR2000029308 http://www.chictr.org.cn/showprojen.aspx?proj=48684 in NEJM 18/03/2020 PMID: 32187464)
ruxolitinib 5688 An approved anti-inflammatory JAK1/2/TYK2 inhibitor. Under clinical evaluation for Covid-19 (in combination with mesenchymal stem cell infusion)
sarilumab 7999 Approved immunosuppressive anti-IL-6 receptor mAb. Four COVID-19 trials underway as of March 30 2020, including the French open-label CORIMUNO-SARI study NCT04324073.
sirolimus 6031 An approved immunosuppressive drug. Sirolimus inhibits MERS-CoV infection of human liver cells in vitro; may be applicable to SARS-CoV-2 infection.
thalidomide 7327 Thalidomide + low-dose glucocorticoid, and thalidomide + celecoxib are two approaches being evaluated for clinical efficacy in patients with severe COVID-19. These combine the immunosuppressive action of thalidomide with the anti-inflammatory actions of glucocorticoids and COX inhibition respectively. See NCT04273529 and NCT04273581 as examples.
tocilizumab 6881 Approved immunosuppressive anti-IL-6 receptor mAb. China's National Health Commission has authorised its use to treat patients with serious COVID-19-induced lung damage, and results have been posted on the preprint server of the Chinese Academy of Sciences. (ChinaXiv), http://www.chinaxiv.org/abs/202003.00026, DOI: 10.12074/202003.00026. Phase 2 trial TOCIVID-19 (NCT04317092) is underway in Italy.
umifenovir (Arbidol) n/a A broad-spectrum antiviral drug used to treat influenza infection in Russia and China; not FDA approved.

Useful Publications

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
This is an outstanding and comprehensive report that identifies interactions between SARS-CoV-2 proteins and human host proteins (the SARS-CoV-2 interactome), and explores the potential for existing FDA drugs to modulate these interactions (either by direct human protein interaction, or with interactions within associated pathways and complexes). It was released to the bioRxiv preprint server, but is from world-renowned labs, and will no doubt soon complete peer review and formal publication.

Other Useful Resources

Additional Reading

WHO: Global research on coronavirus disease (COVID-19)

Latest Coronavirus (COVID-19) research information from NIH: https://www.nih.gov/health-information/coronavirus

Coronavirus (COVID-19): Latest news and resources from the BMJ: https://www.bmj.com/coronavirus

BMJ Best Practice - COVID-19: https://bestpractice.bmj.com/topics/en-gb/3000168

COVID-19 and the cardiovascular system: Zheng et al 2020 Nat Rev Cardiol. PubMed ID: 32139904

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults With Coronavirus Disease 2019 (COVID-19): Alhazzani et al 2020 Intensive Care Med. PubMed ID: 32222812

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor Hoffmann et al. (2020) Cell [Online ahead of print]. PubMed ID: 32142651

Comments on ACE inhibitors and COVID-19; BMJ Rapid Responses to John Watkins’ editorial ‘Preventing a covid-19 pandemic’ https://doi.org/10.1136/bmj.m810

Biocentury article: New vaccines and other therapeutics against COVID-19 that are in development- lists compiled by Biocentury and updated daily.

Dr. Chris Southan's blog: Opening up COVID-19 medicinal chemistry

We published a brief update on coronaviruses in February on our blog.

Live meta-analysis and scrutiny of evidence for all clinical studies that are investigating potential therapeutics for COVID-19 http://www.metaevidence.org/COVID19.aspx

Link to current full list of studies at ClinicalTrials.gov

https://clinicaltrials.gov/ct2/results?cond=&term=coronavirus+OR+COVID-19+OR+nCoV&cntry=&state=&city=&dist=&Search=Search

Links to resources commenting on repurposing efforts

Coronavirus puts drug repurposing on the fast track (Harrison C, Nature 27 Feb 2020) https://www.nature.com/articles/d41587-020-00003-1

Landscape analysis of therapeutics as 17 February 2020 (by the WHO) https://www.who.int/blueprint/priority-diseases/key-action/Table_of_therapeutics_Appendix_17022020.pdf?ua=1

Protein Data Bank in Europe - structures for 'severe acute respiratory syndrome coronavirus 2'

PDBe structures (Organism = severe acute respiratory syndrome coronavirus 2)

UniProt

UniProt release 2020-01 news

SARS-CoV-2 protein sequences from the current public health emergency have been annotated in UniProtKB and made available as a pre-release dataset on the UniProt FTP site. These entries will be available in the usual file formats as part of release 2020_02 (22 April 2020)

UniProt COVID-19 portal - for pre-release SARS-CoV-2 and receptor proteins

Diagnostics pipeline

The Foundation for Innovative New Diagnostics (FIND; in collaboration with the WHO) are conducting an intense programme of work to evaluate new diagnostic tests for SARS-CoV-2 and COVID-19 when asked to do so by manufacturers. Their COVID-19 page provides the latest information and up to date recommendations for laboratory testing. https://www.finddx.org/covid-19/