Coronavirus Information
Last updated: November 2023
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 interaction between the virus and ACE2 on host cells, 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).
NEW: Our manuscript "A Rational Roadmap for SARS-CoV-2/COVID-19 Pharmacotherapeutic Research and Development: IUPHAR Review 29" is now published in the British Journal of Pharmacology, https://doi.org/10.1111/bph.15094. PubMed ID: 32358833
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.
Read the statement from the IUPHAR Clinical Division in Response to the COVID-19 Pandemic.
Cite this page
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/coronavirus.jsp
The development of this page is supported by the International Union of Basic and Clinical Pharmacology (IUPHAR), the British Pharmacological Society (BPS) and by the Wellcome Trust's Institutional Strategic Support Fund, IS3-R201 19/20, which supports COVID-19 work from Drs Jane Armstrong, Elena Faccenda and Christopher Southan.
To cite the IUPHAR/BPS Guide to Pharmacology more generally please refer to our citation page.
- Ligands
- Targets
- Publications
- Resources
Ligands relevant to SARS-CoV-2(COVID-19) - ligand name links to detailed information in GtoPdb.
| Ligand (Therapeutic) | GtoPdb Ligand ID | Comments | |
| dexamethasone |
|
2768 | A widely used and low-cost anti-inflammatory corticosteroid drug. On June 16th 2020, it was reported that results from the UK RECOVERY trial have shown a clear survival benefit of low-dose dexamethasone in COVID-19 patients with severe respiratory complications. It cut the risk of death by a third for patients on ventilators and by 20% for those on oxygen. Dexamethasone does not appear to help patients with milder symptoms of coronavirus. Results have now been submitted to the medRxiv preprint server: Horby et al. (2020) Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report (https://doi.org/10.1101/2020.06.22.20137273). In the UK, dexamethasone was authorised in mid-June 2020 for use within the NHS, as the first coronavirus treatment proven to reduce mortality https://bit.ly/2VPWKuY. |
| 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. Derek Lowe provides a systematic and considered anaylsis of the potential for remdesivir in COVID-19 via his 'In the PIPELINE' blog https://blogs.sciencemag.org/pipeline/archives/2020/04/16/more-small-molecule-clinical-data-against-covid-19-as-of-april-16. Despite limited data on efficacy, the FDA granted full approval in October 2020, for the treatment of hospitalised COVID-19 patients. This was quite unexpected because the FDA based their decision on data from a set of studies that were not suitably designed or controlled. Accumulating data from trials around the world have provided mixed results. It remains the case that larger controlled trials are needed. |
| molnupiravir (EIDD-2801, MK-4482) |
|
10737 | A novel, orally bioavailable RNA-dependent RNA polymerase inhibitor, that targets replication of a wide range of RNA viruses PMID: 32253226; developed by Emory University scientists (originally to treat flu), and being progressed for COVID-19 by Ridgeback Biotherapeutics and Merck. A company press release on 1st October 2021 https://bit.ly/2WAPrLi, revealed that so significant was the clinical benefit of molnupiravir in at-risk, non-hospitalized adult patients with mild-to-moderate COVID-19, the FDA Data and Safety Monitoring Board recommended stopping the trial early, viewing it as unethical to proceed. At a planned interim analysis of data collected from an initial set of >750 participants, molnupiravir reduced the risk of hospitalisation or death by approximately 50% in patients with confirmed mild-to-moderate COVID-19 and at least one risk factor associated with poor disease outcome. However, treatment in a subsequent cohort of ~650 participants was found to be less effective than previously thought. In response to the original efficacy data, Ridgeback/Merck declared their intention to submit applications for approval to various national drug regulatory agencies. Molnupiravir's first approval was issued by the UK's MHRA on 4th Nov. 2021, as a treatment for recently diagnosed SARS-CoV-2 infection in non-hospitalised individuals who have at least one risk factor for developing severe illness. The US FDA recommended molnupiravir for EUA in late November 2021. Approvals by other national regulatory agencies are pending. |
| sotrovimab |
|
11333 | Sotrovimab (VIR-7831) is an anti-spike protein monoclonal antibody that was developed by GSK and Vir Biotechnology as a COVID-19 therapeutic. The UK's MHRA granted full approval for sotrovimab (Xevudy) in October 2021. Under this authorisation it is indicated as a treatment for patients with mild to moderate COVID-19 who have at least one risk factor for developing severe disease. |
| sarilumab |
|
7999 | Approved immunosuppressive anti-IL-6 receptor mAb. It has been under evaluation in COVID-19 trials March 2020. Such trials included the French open-label CORIMUNO-SARI study NCT04324073. Results from an Italian clinical trial were published in July 2020, which concluded that whilst sarliumab accelerated recovery in a subset of patients showing minor lung consolidation at baseline, there was no overall mortality benefit detected in patients with severe COVID-19 compared to standard of care PMID: 32620597. A Phase 2/3 study in the US also failed to meet its primary or secondary endpoints, resulting in study termination (NCT04315298). However, early in 2021, data was reported from a small cohort of severely ill, mechanically ventilated COVID-19 patients in the REMAP-CAP trial (NCT02735707) who received sarilumab. The information released (data not yet published) suggested that sarilumab (compared to standard care) significantly reduced mortality and that patients treated with this mAb were able to leave intensive care 7-10 days earlier than those who didn't receive the drug. |
| tocilizumab |
|
6881 | Tocilizumab is an immunosuppressive anti-IL-6 receptor mAb that is used to treat rheumatoid arthritis. Given the lack of effective antiviral drugs with efficacy against SARS-CoV-2, treating the hyperinflammation in patients with severe COVID-19 was initiated in a number of countries. 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.(ChinaRix), url http://www.chinaxiv.org/abs/202003.00026, DOI: 10.12074/202003.00026. Phase 2 trial TOCIVID-19 (NCT04317092) is underway in Italy. At the end of July 2020 Roche announced that their Ph3 COVACTA RCT (NCT04320615) of tocilizumab in patients with severe COVID-19 pneumonia failed to meet its primary and secondary endpoints (improved clinical status or reduced patient mortality, respectively) https://bit.ly/2Dkp3Lm. They noted a positive trend in time to hospital discharge in the tocilizumab arm. Roche has 3 further ongoing tocilizumab studies in COVID-19, Ph3s REMDACTA (NCT04409262 tocilizumab + remdesivir) and EMPACTA (NCT04372186), and Ph2 MARIPOSA (NCT04363736). Results published in The Lancet in August 2020, from an observational study, showed a reduction in mortality associated with low-dose tocilizumab in COVID patients with confirmed inflammatory markers doi.org/10.1016/S2665-9913(20)30277-0. This is in apparent contradiction to the COVACTA results. The limitations and differences between the studies, and reasoning that might explain the conflicting results are discussed by Campochiaro and Dagna (2020) doi.org/10.1016/S2665-9913(20)30287-3. There may still be hope for tocilizumab, if used in the right patients at the right time. Indeed, this seems to be coming to fruition, with Roche stating that in their EMPACTA study the addition of tocilizumab to standard of care significantly reduced (by 44%) the number of COVID-19 pneumonia patients who progressed to mechanical ventilation or who died (https://bit.ly/35UNGKY, not yet published). In addition, early in 2021, data was reported from a small cohort of severely ill, mechanically ventilated COVID-19 patients in the REMAP-CAP trial (NCT02735707) who received tocilizumab. The information released (data not yet published) suggested that tocilizumab (compared to standard care) significantly reduced mortality and that patients treated with this mAb were able to leave intensive care 7-10 days earlier than those who didn't receive the drug. This effect appears to be in addition to the clinical benefit conferred by dexamathasone. As a result of this latest report, the UK Department of Health and Social Care issued updated guidance (on 8th Jan) which encouraged NHS trusts across the UK to immediately begin using existing stocks of tocilizumab in their treatment of critically ill COVID-19 patients in ICUs. Outcomes from the RECOVERY trial tocilizumab arm were announced on 11th Feb 2021, and a preprint manuscript was submitted to medRxiv https://bit.ly/3afLLCK - the analysis showed that tocilizumab improved survival and other clinical outcomes (in addition to systemic corticosteroid therapy) and that this efficacy was independent of the level of respiratory support patients required. |
| Ronapreve (imdevimab + casirivimab; REGN-COV2) |
/ -
|
11327 / 11328 | This is a cocktail of neutralising monoclonal antibodies that bind spike protein and block SARS-CoV-2 entry into host cells. Granted FDA EUA in Nov. 2020 and approved by the Japanese Ministry of Health, Labour and Welfare in July 2021 (based on NCT04425629), and then by the UK's MHRA in August 2021. Awaiting publication of results from the RECOVERY trial. |
| Abl kinase inhibitors (e.g. imatinib) |
|
5687 | Abelson kinase (Abl) inhibitors are reported to block Spike protein-induced SARS-CoV and MERS-CoV fusion in vitro PMID: 29557770, potentially by blocking Abl2 at the endosomal membrane PMID: 27466418. It will be informative to determine if this holds true for SARS-CoV-2, and whether re-purposing of imatinib and/or newer Abl kinase inhibitors (dasatinib; bosutinib) could be a viable strategy against COVID-19. Likely to be most effective during the early stage of infection. |
| acalabruntinib |
|
8912 | Acalabrutinib is an approved BTK inhibitor that is used to treat B cell malignancies. It is being progressed to clinical trial in COVID-19 patients as part of the UK's ACCORD initiative https://bit.ly/2ZXjXOw. Preliminary data from off-label use in the US suggests that acalabrutinib therapy normalises markers of inflammation (CRP, IL-6) in patients with severe COVID-19, and that targeting host hyperinflammation via BTK inhibition is a rational therapeutic strategy can improve patient outcomes in this disease (https://pubmed.ncbi.nlm.nih.gov/32503877). |
| ACE2 ligands | - | n/a | ACE2 ligands that block the site of viral spike protein interaction could offer anti-SARS-CoV-2 infection potential. In hypertensive COVID-19 patients maintained on ACE2 inhibitor therapy whilst hospitalised, ACE2 inhibitors are reported to reduce all-cause mortality compared to patients with hypertension not on ACE inhibitors PMID: 32302265. But we need to be cognisant that the protective effects may not be evident in COVID-19 patients with normal blood pressure, and that a proper controlled clinical trial is needed before drawing firm conclusions. |
| acebilustat | - | 11984 | Acebilustat (CTX-4430) is a clinical stage leukotriene A4 hydrolase (LTA4H) inhibitor. It mediates anti-inflammatory effects by disrupting biosynthesis of the pro-inflammatory mediator leukotriene B4. Being investigated for efficacy in COVID-19 inflammation. |
| ADG20 | - | n/a | Adagio Therapeutics have identified an anti-coronavirus mAb (ADG20) with broad-spectrum neutralising activity. The epitope for this mAb resides on the spike protein, at a position that overlaps, but is distinct from the target of other mAbs that interact at spike's receptor binding domain (RBD). This novel epitope is present in sarbecoviruses (SARS-CoV and SARS-CoV-2) and some coronaviruses circulating in bats, indicating that ADG20 has potential against existing human coronaviruses, and those that may emerge in the future. PMID: 33495307 contains further details. ADG20 is in Phase 2/3 clinical trial (NCT04805671). |
| alunacedase alfa | - | 11320 | Evidence that supports the strategy of using recombinant ACE2 protein (rhACE2) as a decoy/soluble trap for SARS-CoV-2 is published in PMID: 33093202 and PMID: 33144565. Alunacedase alfa is the INN requested by Apeiron Biologics for their rhACE2 agent APN01, which is a well advanced clinical lead for COVID-19. Phase 2 study NCT04335136 is using a composite primary endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge to determine efficacy. |
| ambrisentan |
|
3951 | Ambrisentan is a widely used endothelin receptor antagonist. It is being assessed in hospitalised COVID-19 patients for potential to ease SARS-CoV-2 infection-induced endothelial cell damage and dysfunction in the lungs and other organs. |
| AMY-101 | - | 11986 | AMY-101 is a clinical stage compstatin-based complement C3 inhibitor. It has been entered into clinical trials that aim to determine its ability to combat the dysregulated immune response that drives organ damage (lung and other organs) in patients with severe COVID-19- Phase 2 NCT04395456. A single COVID patient has previously been safely and successfully treated with AMY-101 PMID: 32360516 |
| anakinra |
|
6972 | An approved IL-1 pathway blocking peptide, that has anti-inflammatory action. This Comment in The Lancet Rheumatology discusses factors to be considered when planning anakinra trials for COVID-19 hyperinflammatory response https://bit.ly/2yu89Ig. |
| anti-TNF therapy (e.g. infliximab, adalimumab and others) |
/ -
|
5004 / 4860 | The case for re-purposing approved anti-TNF biologic therapies as a means to combat cytokine storm and inflammation in COVID-19 patients is presented in PMID: 32278362. |
| apabetalone | - | 7034 | Apabetalone (RVX 208) is a clinical stage, oral BRD-targetting BET inhibitor that was developed as a treatment for diabetes, atherosclerosis, and coronary artery disease. In response to the SARS-CoV-2 pandemic, this agent was repositioned for potential to provide a cardio-protective therapy that prevents COVID-19-mediated cardiac damage. |
| apilimod | - | 9859 | Apilimod is a clinical stage inhibitor of the type III phosphoinostol kinase, PIKfyve. It has anti-SARS-CoV-2 activity in vitro PMID: 32707573. One note of caution for clinical trial of apilimod in COVID-19 patients (NCT04446377): PIKfyve has been implicated as a key component of antigen presentation by dendritic cells and the immune response to new antigens PMID: 30612035. If apilimod were to interfere with this crucial immune response in a setting of ongoing infection, the outcome could be less than ideal. Could it also leave patients more suceptible to other infections during treatment? |
| apremilast |
|
7372 | Apremilast is an approved phosphodiesterase 4 (PDE4) inhibitor that reduces inflammatory cytokine production by T-cells. It is included in the collaborative I-SPY COVID adaptive clinical trial that was initiated in the US in July 2020. Apremilast will be tested for potential to reduce life-threatening immune hyperactivation that manifests in some serious COVID-19 patients. |
| asapiprant | - | 11951 | Asapiprant is a clinical stage prostaglandin DP1 receptor antagonist. It was originally intended for use as an anti-inflammatory drug for allergic inflammation. It has been repurposed for potential to reduce inflammation in confirmed COVID-19 patients who are older than 50, who are hospitalised but who aren't yet in respiratory failure (currently Phase 2). |
| 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. |
| ATYR1923 | - | n/a | ATYR1923 is a clinical stage neuropilin-2 (NRP2)-targeting immunomodulator being developed for acute lung injury associated with pulmonary sarcoidosis. It is now being applied to COVID-19 ARDS. |
| aviptadil |
|
10891 | A VIP analogue, VPAC1 receptor agonist that is already in clinical use. Preclinical and clinical experience shows that aviptadil restores function in pulmonary hypertension, ARDS, and acute lung injury (ALI), reduces IL-6 and TNFalpha production, and protects against pulmonary edema. This combination of benefits has led to aviptadil being investigated as a treatment option for ARDS in COVID-19 patients (NCT04311697). |
| AZD7442 (cilgavimab + tixagevimab) |
/ -
|
11329 / 11330 | AZD7442 is a cocktail of two long acting anti-spike monoclonal antibodies. It has reached Phase 3 evaluations a pre- and post-exposure prophylaxis of COVID-19 in adults. AZD7442 is proposed for therapeutic potential in individuals who are likely to respond poorly to SARS-CoV-2 vaccines, or who cannot be vaccinated for any reason, including those who are immunocompromised. Positive results as pre-exposure prophylaxis were announced by press release in August 2021, but the full data have yet to be published. |
| AZD7986 (INS1007, brensocatib) | - | 9412 | AZD7986 inhibits activation of neutrophil elastase via direct inhibition of dipeptidyl peptidase 1, that is being investigated as a treament for neutrophilic lung inflammation. It has been shown to produce on-target effects in healthy trial volunteers (PMID: 29484635). Plans are underway to examine the potential of AZD7986 (now being progressed by Insmed as INS1007) to treat COVID-19-related acute respiratory distress syndrome (ARDS), in the UK STOP-COVID19 clinical trial. The INS1007 arm of the study aims to administer the drug to 150 COVID-19 patients (plus 150 in the placebo arm) across 10 UK hospitals. |
| baricitinib |
|
7792 | Baricitinib is an oral JAK inhibitor with anti-inflammatory action that is usually used to treat RA. Several clinical studies have examined the efficacy of baricitinib as a mechanism to reduce the pathological over-active immune response in COVID-19 patients with severe symptoms. The combination of baricitinib plus remdesivir vs. remdesivir alone was evaluated in the Adaptive COVID-19 Treatment Trial 2 (ACTT-2) study NCT04401579, which began in May 2020. In mid-September 2020 baricitinib's manufacturer Eli Lilly published a press release which claimed that the drug combination decreased median recovery time across all COVID-19 patients treated, by one day, compared to remdesivir monotherapy (link to the press release https://bit.ly/3hxAY77). This combination was issued with an FDA EUA in Nov. 2020. On 2nd Feb. 2021, a baricitinib + standard of care vs. standard of care arm was added to the University of Oxford-led RECOVERY trial (more details on the RECOVERY website https://bit.ly/2MiDHYN). Data from RECOVERY that was announced in March 2022, confirmed the existing evidence that baricitinib is beneficial in severe COVID-19, and demonstrated that its clinical benefit was observed in addition to standard care treatments including dexamethasone, tocilizumab or remsesivir. |
| bemcentinib | - | 10478 | Bemcentinib is an investigational, selective and orally active AXL receptor tyrosine kinase inhibitor. Part of its mechanism of action is to inhibit proinflammatory cytokine production. It is being progressed to clinical trial in COVID-19 patients as part of the UK's ACCORD initiative https://bit.ly/2ZXjXOw, to determine if its anti-inflammatory action is efficacious in combating COVID-19 associated hyper-inflammatory response. |
| β-D-N4-hydroxycytidine | - | 10735 | Experimental evidence indicated that EIDD-1931's prodrug molnupiravir/EIDD-2801 exhibited broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs PMID: 32253226. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlighted its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses. |
| 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. |
| BIO101 | - | 11987 | BIO101 is pharmaceutical grade 20-hydroxyecdysone and it is a clinical stage non-peptidic activator of the class A orphan GPCR MAS1. In COVID-19 patients it is predicted to a promote a MAS receptor-mediated activation of the protective arm of the RAS, to combat disruption of the ACE2-RAS pathway by SARS-CoV-2 spike protein/ACE2 binding. |
| boceprevir |
|
7876 | Boceprevir has a history of use in humans to treat HCV infections. It inhibits the HCV NS3/4A viral protease. Repurposing screens have shown that boceprevir inhibits SARS-CoV-2 Mpro. Peer reviewed data is available from PMIDs: 33524017 and 32541865 |
| brequinar | - | 7406 | A clinical stage DHODH inhibitor, that inhibits SARS-CoV-2 replication in vitro PMID:32754890; has entered Phase 1/2 clinical evaluation in COVID-19 patients (NCT04425252). |
| 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. |
| bromhexine |
|
11218 | Bromhexine is a widely used mucolytic drug. It is a prodrug of ambroxol. Clinical trials in patients with COVID-19 are underway in a number of countries including Iran, Russia, Slovenia, China and Mexico. |
| budesonide |
|
7434 | Budenoside is a long-used anti-asthmatic inhaled glucocorticoid drug. Results from Phase 2 NCT04416399 show that administration of budesonide in the early phase of SARS-CoV-2 infection reduces both the likelihood of needing urgent medical care and time to recovery PMID: 33844996. |
| camostat |
|
6432 | Serine protease inhibitor with activity against the host TMPRSS2 protease that is exploited by SARS-CoV-2 to mediate viral entry. There are a number of clinical trials underway in dfferent countries that are evaluating camostat's ability to reduce progression of COVID-19 symptoms in newely diagnosed, non-hospitalised patients. One of these is the Phase 2/3 SPIKE-1 trial (NCT04455815; Edinburgh University, CRUK and Latus Therapeutics) that began in August 2020 - https://bit.ly/2Tza6dr |
| 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. |
| canakinumab |
|
6773 | Canakinumab is an approved anti-IL-1beta mAb drug so clinical safety is established. It has been entered in to clinical trials that aim to determine its ability to combat the exaggerated immune response that drives cytokine storm and leads to tissue damage in the lung and other organs in patients with severe COVID-19. |
| cenicriviroc | - | 801 | Cenicriviroc is an experimental nonalcoholic steatohepatitis drug that is an antagonist of the CCR2 and CCR5 chemokine receptors, which are linked to acute respiratory distress syndrome in COVID-19. It is included in the collaborative I-SPY COVID adaptive clinical trial that was initiated in the US in July 2020. Cenicriviroc will be tested for potential to reduce life-threatening immune hyperactivation that manifests in some serious 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). |
| clazakizumab | - | 9195 | Clazakizumab is a clinical stage anti-IL-6 mAb. It has been entered into clinical trials in patients with COVID-19, with a focus on assessing its efficacy in those with life-threatening hyperinflammation. |
| clofazimine |
|
9184 | Clofazimine is a leprosy drug that has a long history of use in humans. In a repurposing study it was discovered to have in vitro and in vivo anti-coronavirus activity, that seems to arise by targeting SARS-CoV-2 replication at multiple steps (reducing spike-mediated cell fusion, and viral helicase activity) PMID: 33727703. Clofazimine has advanced to clinical trial in combination with IFN-1b (NCT04465695), and plans are underway to progress to Phase 2 as a monotherapy and in combination with remdesivir. |
| colchicine |
|
2367 | Colchicine is an approved drug, so safety in humans is established. It is administered orally, and is used to treat gout and autoinflammatory diseases. Colchicine was predicted to target inflammation and systemic clotting abnormalities that accompany COVID-19 and was entered into clinical trials (https://bit.ly/3eBTB8G) that aimed to evaluate its efficacy as a therapy to help treat, and/or prevent the development of uncontrolled inflammation and severe clotting abnormalities that occur in COVID-19 patients. In early 2021, preliminary data from >4100 confirmed COVID-19 patients recruited to the ColCORONA study (NCT04322682) provided some indications that colchicine reduced hospitalisation (by 25%), progression to mechanical ventilation (by 50%) or death (by 44%), compared to placebo. The drug was given to patients at home. Preprint was posted online on 27 Jan (https://bit.ly/2McLN4P) to share the data, prior to completion of the peer review process. A preprint of results from the colchicine arm of the RECOVERY trial reported no clinical efficacy compared to standard care medRxiv (Horby et al.,https://doi.org/10.1101/2021.05.18.21257267) |
| 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. |
| compound 1b [PMID: 37562607] | - | 13028 | This compound is an experimental inhibitor of SARS-CoV-2 nsp13 (helicase). Inhibiting nsp13 is proposed to elicit an antiviral effect |
| compound 25 [PMID: 35439007] | - | 11971 | An experimental SARS-CoV-2 nsp14 inhibitor. The methyltransferase (MTase) activity of nsp14 is required for capping of the viral RNA transcript. Inhibition of this activity should disrupt viral replication. Compound 25 is selective for nsp14 compared to human RNA N7-MTase (RNMT). |
| compound 4b [Ramsey et al., 2023] | - | 13022 | This compound is an experimental inhibitor of SARS-CoV-2 nsp13 (helicase). Inhibiting nsp13 is proposed to elicit an antiviral effect |
| conestat alfa (Ruconest) | - | n/a | Conestat alfa is an approved drug. It is a recombinat version of human C1 esterase inhibitor protein, that was designed to modulate the inflammatory response mediated via the complement system. Its developer, Pharming Group N.V., has reported preliminary results of successful treatment of 5 severe COVID-19 patients with conestat alfa (albeit with no placebo group). Pharming's press release (of 21 April 2020) indicates that a multinational RCT in a larger number of patients is being planned https://bit.ly/2WOAp0A. |
| CPI-006 | - | n/a | Corvus Pharmaceuticals have a clinical stage, agonistic (immunostimulatory) CD73-targeting mAb (CPI-006; developed as an immuno-oncology agent) that is able to promote B cell activation, lymphocyte trafficking (and production of antigen-specific IgM and IgG antibodies), and to elevate numbers of memory B cells. CPI-006 is being repositioned as a novel immunotherapy approach that is predicted to provide both immediate (e.g. shortened recovery time) and long-term (e.g. improved protective immunity) clinical benefits for (hospitalised) COVID-19 patients; Phase 1 clinical trial NCT04464395. |
| danicopan |
|
11988 | Danicopan (ACH-4471) is a clinical stage oral, direct inhibitor of the protease activity of complement factor D. It prevents activation of the alternative complement pathway. Danicopan is being tested in COVID-19 patients to evaluate the therapeutic effect of blocking the alternative complement pathway on COVID-19-related tissue damage. |
| dapagliflozin |
|
4594 | An approved sodium/glucose cotransporter (SGLT2) inhibitor used to treat T2DM. Based on the cardio- and renoprotective benefits of dapagliflozin in T2DM patients, it was evaluated vs. placebo in 1250 hospitalised COVID-19 patients (NCT04350593) PMID: 33319454, to determine if it would provide similar protection from organ damage caused by SARS-CoV-2 infection. The drug treatment effected a non-significant reduction in the risk of organ failure or death of one-fifth PMID: 34302745 |
| dapansutrile | - | 10056 | Dapansutrile (OLT1177) is a clinical stage NLRP3 inflammasome inhibitor whose immunomodulatory potential is being evaluated in a number of inflammation conditions. |
| darunavir + cobicistat |
/ -
|
11243 / 7535 | Antiretroviral, protease inhibitor. Cobicistat increases its bioavailability and half life. Phase 3 NCT04252274 for COVID-19. |
| DX600 | - | 11602 | DX600 is a peptide that binds to angiotensin-converting enzyme 2 (ACE2). Experiments using lab-grown, human embryonic stem cell-derived beating cardiomyocytes have demonstrated that DX600 can prevent pseudotyped SARS-CoV-2 from entering the heart cells https://pubmed.ncbi.nlm.nih.gov/34326460. This research indicates that agents that physically block spike-ACE2 binding could be leveraged as novel infection preventatives, that also offer the potential to reduce SARS-CoV-2-mediated damage to heart tissue. |
| eculizumab |
|
6884 | Eculizumab is an approved anti-C5 mAb drug so clinical safety is established. It has been entered into clinical trials that aim to determine its ability to combat the dysregulated immune response that drives organ damage (lung and other organs) in patients with severe COVID-19. |
| emapalumab |
|
9295 | Emapalumab is an approved anti-IFNgamma mAb drug so clinical safety is established. It has been entered in to clinical trials that aim to determine its ability to combat the exaggerated immune response that drives cytokine storm and leads to tissue damage in the lung and other organs in patients with severe COVID-19. |
| empagliflozin |
|
4754 | An approved sodium/glucose cotransporter (SGLT2) inhibitor used to treat T2DM. Added to the RECOVERY trial in July 2021 (https://bit.ly/3l6f4x5), to determine if using empagliflozin to correct metabolic dysregulation caused by SARS-CoV-2 infection can protect against organ damage and improve recovery in COVID-19 patients. |
| emtricitabine + tenofovir |
/ -
|
11244 / 10948 | NRTI/NtRTI anti-HIV combination that could be repurposed for COVID-19. |
| emvododstat | - | 11421 | Emvododstat (PTC299) is a clinical stage dihydroorotate dehydrogenase (DHODH) inhibitor that suppresses noncanonical ribosomal translation that is switched on in cells under stress conditions (hypoxia, oncogenic transformation and viral infection). It has been shown to inhibit replication of RNA viruses in vitro, and to reduce inflammatory cytokine production in SARS-CoV-2 infected cells. It has been redeployed as a potential COVID-19 therapy (Phase 2/3 NCT04439071). |
| 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). |
| ensitrelvir |
|
11871 | Ensitrelvir (S-217622) is a Mpro inhibitor that was developed by Shiongi as an anti-coronavirus drug. It was approved for use in Japan in November 2022. |
| ensovibep (MP0420) | - | 11470 | MP0420 is a DARPin that binds to the SARS-CoV-2 spike glycoprotein, and offers virus neutralising potential. It is being progressed to clinical trial by Molecular Partners and Novartis. DARPins are protein-based therapeutics, with the high selectivity and affinity of antibodies, but are around 10% of the size. They are easier to manufacture than whole antibodies, and may be suitable for subcutaneous administration rather than infusion. Molecular Partners have developed two multi-valent DARPins that are designed to engage multiple sites of the SARS-CoV-2 spike glycoprotein. Novartis and Molecular Partners are working together on both MP0420 and MP0423 for COVID-19. |
| ezurpimtrostat | - | 11991 | Ezurpimtrostat (GNS561) is a small molecule inhibitor of palmitoyl-protein thioesterase 1 (PPT1). It induces lysosomal dysregulation which leads to inhibition of late-stage autophagy and cell death. Antitumour and antiviral activities have been demonstrated in vitro and in vivo. Anti-SARS-CoV-2 activity is being investigated in Phase 2 clinical trial NCT04637828. |
| favipiravir |
|
11139 | 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. |
| gimsilumab | - | 9624 | An anti-GM-CSF (CSF2) mAb currently in clinical trial for anti-inflammatory potential in the treatment of autoimmune inflammation and cancer. Has been repurposed for deranged inflammation in COVID-19 (Phase 2, NCT04351243). |
| GLS-5300 | - | n/a | A Phase 1 MERS vaccine. |
| heparin |
|
4214 | Heparin is being used in ICU settings (based on observational efficacy) to mitigate against COVID-19-associated thromboembolic events (heart attack, stroke, pulmonary embolism). It is being progressed to clinical trial in COVID-19 patients as part of the UK's ACCORD initiative https://bit.ly/2ZXjXOw. Experimental evidence suggests that heparin (and non-anticoagulant heparan sulfate) directly binds the coronavirus, so could potentially be administered as a decoy to neutralise the virus before it can infect healthy cells via ACE2 PMID: 32653452. |
| hydroxychloroquine |
|
7198 | An existing antimalarial drug, with in vitro activity against SARS-CoV (PMID: 16640347). Extreme caution must be taken when condisering using hydroxychloroquine (HCQ) as it has severe cardiac adverse effects, and in addition its distribution to lung tissue is unknown. There was much hype around repositioning HCQ to treat COVID-19. But this was based on preliminary evidence from a small cohort of COVID-19 patients in a VERY small study (PMID: 32205204). There was also a lot of controversy around some of the larger scale trials, how they were carried out, and how they were reported or published. Results from subsequent well run, well powered, large scale RCTs does not support any clinical benefit from HCQ in COVID-19 patients. Derek Lowe's 'In the PIPELINE' blog https://bit.ly/31C7DT1 provides a systematic and considered anaylsis of the (lack of) potential for hydroxychloroquine/chloroquine for COVID-19. |
| I-432 | - | 10733 | An in vitro tool compound; inhibitor of serine protease TMPRSS2. |
| IC14 | - | n/a | IC14 is a chimeric mAb directed against human CD14. Because of its key role in amplifying the immune response, CD14 has been targeted for pharmacological modulation. In April 2020, in response to the COVID-19 pandemic, Implicit initiated a clinical trial (NCT04346277) to investigate the potential of CD14 modulation as a mechanism to mitigate against cytokine storm and ARDS in patients with this potentially deadly disease. |
| icatibant |
|
667 | Icatibant is a long-established drug used to treat hereditary angioedema, by inhibiting the receptor for the inflammatory molecule bradykinin. It is included in the collaborative I-SPY COVID adaptive clinical trial that was initiated in the US in July 2020. Icatibant will be tested for potential to reduce life-threatening immune hyperactivation that manifests in some serious COVID-19 patients. |
| IFN-β (interferon beta) | - | 4967 | Recombinant formulations of IFN-beta are used to treat multiple sclerosis (MS), so safety has been established. IFN-beta is a key modulator of immune defence against viruses. The coronavirus seems to suppress production of types I and III IFNs (IFN-beta is a type I IFN) as part of its strategy to evade immune detection and destruction (Blanco-Melo et al., 2020 In press. DOI: 10.1016/j.cell.2020.04.026). Administering exogenous IFN-beta directly to the lungs is predicted to re-engage the anti-viral immune response to SARS-CoV-2. One such formulation is SNG001 (Synairgen Research) that can be delivered directly to the lungs via a nebuliser. SNG001 was initially designed to treat viral infection-related exacerbations in COPD patients (currently in Phase 2), but has been rapidly re-deployed for coronavirus infection. Phase 2 (NCT04385095) safety and efficacy data was published in November 2020 in The Lancet Respiratory Medicine https://bit.ly/3prXoMr. This study found that, compared to placebo, SNG001 reduced time to recovery and increased chances of improvement in hospitalised COVID-19 patients. The results warrant progressing SNG001 to larger scale trials. |
| isuzinaxib | - | 11985 | Isuzinaxib (APX-115) is a pan-NADPH oxidase (NOX) inhibitor that is proposed to inhibit ROS production. It is being evaluated for potential to reduce ROS-induced tissue damage as a result of SARS-CoV-2 infection. |
| lanadelumab |
|
9094 | Landelumab acts to inhibit the plasma kallikrein-bradykinin axis. It is being investigated as an option to reduce the elevated level of vasodilatory bradykinin which has been detected in COVID-19 patients, and that has been proposed to underlie many of the common symptoms of the infection (see New Scientist Health article of 8th Sep 2020 https://bit.ly/35WtyIs) |
| lenzilumab | - | 8935 | Lenzilumab has been entered into clinical trial to determine if blocking GM-CSF signalling can help to alleviate the immune-mediated cytokine release syndrome in patients with severe or critical COVID-19 pneumonia. The aim would be reduce the time to recovery in hospitalised patients. |
| leronlimab | - | 10752 | A clinical stage anti-CCR5 mAb with immunomodulatory potential. This was evaluated in Ph3 clinical trials in COVID-19 patients as a strategy to reduce cytokine storm and related pathophysiological sequelae, but the study failed to meet its primary goal (reducing symptoms) and all of its secondary goals (including reducing mortality). |
| MDL-28170 | - | 10745 | Anti-SARS-CoV-2 activity in vitro PMID: 32707573 |
| MEDI 3506 | - | n/a | MEDI 3506 is an investigational anti-IL-33 mAb that is being developed for anti-inflammatory potential. It is being progressed to clinical trial in COVID-19 patients as part of the UK's ACCORD initiative https://bit.ly/2ZXjXOw. |
| meplazumab | - | 11026 | 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. |
| MK-7110 | - | 11395 | A clinical stage synthetic fusion protein and CD24 mimetic, that enhances CD24/SIGLEC10 suppression of DAMP-triggered activation of the immune response and associated tissue damage. Repositioned to combat COVID-19 inflammation, reaching Phase 3, but development was discontinued in April 2021. |
| mucolytic drugs |
|
10692 | Ambroxol is an approved mucolytic which has the potential to combat pulmonary congestion in numerous lung conditions. |
| N-0385 | - | 11956 | A serine protease inhibitor, originally reported as a matriptase inhibitor and more recently revealed to inhibit SARS-CoV-2 infection via inhibition of TMPRSS2 (the host protease hijacked by the coronavirus to cleave spike and facilitate entry into host cells), thus functioning as an 'entry inhibitor'. The Nature article (DOI: 10.1038/s41586-022-04661-w) proposes prophylactic and therapeutic potential, as well as pan-coronavirus efficacy that is independent of virus strain. May have applications in combination with antivirals with other MMOAs e.g. Mpro or RdRp inhibitors. |
| nafamostat |
|
4262 | A protease inhibitor approved in Japan. Now being evaluated in combination with favipiravir in a RCT in patients with COVID-19 pneumonia (clinical trial number jRCTs031200026). Nafamostat is being proposed to reduce SARS-CoV-2 entry by inhibiting the host protease TMPRSS2 [PMID:27550352], and to additionally counteract COVID-19-associated thrombosis via its established anticoagulant activity. |
| nirmatrelvir (PF-07321332) |
|
11503 | PF-07321332 is an oral SARS-CoV-2 3CL protease (Mpro) inhibitor, and clinical lead compound from Pfizer. Inhibiting Mpro actvity blocks replication at an early stage in the virus' life cycle, and due to structural similarities between the Mpro's of other coronavirusus, PF-07321332 offers the potential of pan-coronavirus activity. In vitro it is reported to inhibit replication of CoV-2 variants, including delta and omicron. PF-07321332 was progressed to clinical trial to determine safety and efficacy as a treatment for COVID-19. Phase 1 (NCT04756531) results were published in Science, in early November 2021 DOI: 10.1126/science.abl4784. A few days after the Phase 1 results were published, Pfizer announced that interim analysis from their Phase 3 EPIC-HR study (NCT04960202), indicated that PF-07321332 (in combination with ritonavir, with the trade name Paxlovid) reduced the risk of hospitalisation or death by almost 90% in patients who were at high risk of progressing to severe illness, and who were treated within 3 days of symptom onset https://bit.ly/3wxA5of. Pfizer have reported that PF-07321332 reduces viral load in trial participants by 10-fold, which suggests the potential for reduced transmission. Full trial data has yet to be formally published. |
| ONO-5334 | - | 10747 | Anti-SARS-CoV-2 activity in vitro PMID: 32707573 |
| OP-101 | - | n/a | OP-101 (Orpheris/Ashvattha Therapeutics) is a novel, clinical stage anti-inflammatory agent. Chemically, it is a metabolically-stable inactive dendrimer covalently conjugated to N-acetyl cysteine (NAC). OP-101 was developed to specifically target activated immune cells in the brain to block neuroinflammatory demyelination in diseases such as X-linked adrenoleukodystrophy. It has the ability to target reactive macrophages, in which release of NAC into the cells reduces oxidative stress, blocks production of pro-inflammatory cytokines and attenuates inflammation. This action has led to OP-101 being accepted for Phase 2 clinical trial in patients with severe COVID-19 disease https://bit.ly/36YoPVa. Scientific data supports the proposition that OP-101 could modulate the hyperinflammation, cytokine storm and subsequent tissue damage that underlies much of COVID-19's fatal effects. |
| opaganib | - | 6624 | Opaganib is an orphan drug that is in Phase 2 evaluation. A medRxiv preprint descibes the compassionate use of opaganib in a small cohort of patients with severe COVID-19 (https://www.medrxiv.org/content/10.1101/2020.06.20.20099010v1), predicated upon the drug's anti-inflammatory and anti-viral properties. Results analysis indicated trends in favour of clinical efficacy which led to extended investigation in a Phase 2 randomised placebo-controlled trial in patients with COVID-19 pneumonia. |
| 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. |
| otilimab | - | 11132 | Otilimab is a Ph3 anti-GM-CSF mAb with anti-inflammatory action. It is being investigated in a Ph2 RCT, in patients with severe COVID-19, as a mechanism to reduce severe inflammatory lung complications, improve lung function and potentially improve clinical outcomes NCT04376684 (ISRCTN18205700) |
| PF-07304814 | - | 11249 | PF-07304814 is a SARS-CoV-2 3CL protease (Mpro) inhibitor from Pfizer. It is being advanced to Phase 1 evaluation (NCT04535167) to determine its clinical safely and preliminary antiviral efficacy. |
| 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). |
| ravulizumab |
|
10168 | Ravulizumab is an approved anti-C5 mAb drug so clinical safety is established. It has been entered into clinical trials that aim to determine its ability to combat the dysregulated immune response that drives organ damage (lung and other organs) in patients with severe COVID-19. |
| 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 + 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 | This is a clinically used, orally administered anti-HIV combination drug therapy, so safety has been established.Two separate clinical trials have reported no clinical efficacy for this medication in severe COVID-19; No significant benefit, 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 https://pubmed.ncbi.nlm.nih.gov/32187464). The UK RECOVERY trial also reported lack of efficacy for this combo in late June 2020 https://bit.ly/2YMwHGH. The RECOVERY team noted that it was impossible to study a large number of patients on invasive mechanical ventilation because the oral mode of delivery was incompatible with invasive ventilation. |
| ruxolitinib |
|
5688 | An approved anti-inflammatory JAK1/2/TYK2 inhibitor. Under clinical evaluation for COVID-19 (in combination with mesenchymal stem cell infusion) |
| selinexor |
|
10036 | An approved drug that acts as a selective inhibitor of nuclear export (SINE). SINE compounds have been shown to disrupt the replication of multiple viruses in vitro and in vivo and to mediate anti-inflammatory and anti-viral effects in animal models. In respect of SARS-CoV-2, SINE compounds have been reported to exhibit potential to interfere with interactions between viral proteins and key host proteins [PMID:32353859]. Based on this in vitro observation, low-dose selinexor has been advanced to Phase 2 investigation in patients with severe COVID-19 (NCT04349098). |
| siltuximab |
|
7396 | Siltuximab is an approved anti-IL-6 mAb drug so clinical safety is established. It is being repositioned for potential to combat cytokine storm resulting from an exaggerated response of the immune system in patients with severe COVID-19. |
| 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. |
| tipiracil |
|
8696 | Tipiracil (an approved drug, a uracil derivative) has been shown to bind to the uridine-specific endoribonuclease Nsp15 of SARS-CoV-2, and this interaction inhibits the enzyme's uridine-degrading catalytic activity. Anti-coronavirus activity has not yet been demonstrated. |
| TO507 | - | 11981 | TO507 is an experimental SARS-CoV-2 nsp14 inhibitor. The methyltransferase (MTase) activity of nsp14 is required for capping of the viral RNA transcript. Inhibition of this activity should disrupt viral replication. |
| TRV027 | - | 6902 | TRV027 was a clinical candidate for heart failure that was studied through to Phase 2b, so has been tested in humans. A clinical trial (NCT04419610; Imperial College London) has been designed to establish if antagonising the renin-angiotensin system with TRV027 has efficacy to combat acute lung injury and ARDS in COVID-19 patients. If successful this would offer an additional option to anti-virals and anti-inflammatory therapies to address the umet clinical need for treating this multi-system, multi-organ disease. |
| umifenovir (Arbidol) | - | n/a | A broad-spectrum antiviral drug used to treat influenza infection in Russia and China; not FDA approved. |
| uproleselan | - | 11995 | Uproleselan (GMI-1271) is a clinical stage selectin E inhibitor. As a potential treatment for COVID-19, uproleselan-mediated antagonism of selectin E binding is predicted to reduce leukocyte migration & trafficking to the inflamed lungs. |
| ursodeoxycholic acid |
|
7104 | UDCA is a widely used drug. UDCA attenuates bile acid-induced, FXR-mediated upregulation of ACE2 expression in vitro and in vivo PMID: 36470304. For this effect, UDCA has been proposed as a repurposing drug with antiviral potential against SARS-CoV-2. It is hypothesised that UDCA would reduce SARS-CoV-2 infection potential by lowering the number of ACE2 binding sites on relevant tissues. In support of this theory, a correlation between UDCA treatment for liver conditions and a lower risk of developing severe COVID-19 has been identified |
| VBY-825 | - | 10746 | Anti-SARS-CoV-2 activity in vitro PMID: 32707573 |
| VHH72-Fc | - | n/a | VHH72-Fc is a preclinical Llama-derived anti-SARS-CoV-2 single-domain antibody (VHH) that is being developed by ExeVir Bio. It targets the virus' spike protein, and cross-reacts with SARS-CoV-1 spike. VHHs are suitable for nebulisation and inhaler administration, which positions them well for the treatment of respiratory diseases such as COVID-19. |
| vidofludimus | - | 9860 | Vidofludimus is a clinical stage immunosuppressive drug that acts through inhibition of dihydroorotate dehydrogenase (DHOD). It is being evaluated in clinical trial as an oral agent to reduced the hyperinflammatory response in hospitalised COVID-19 patients. Also being tested in combination with oseltamivir (Tamiflu) in UK hospitals. |
| vorapaxar |
|
4047 | An approved anti-thrombotic drug. Rationale for potential to combat COVID-19-associated thrombosis and endotheliitis is provided in PMID: 32639031 |
| zapnometinib | - | 11679 | Zapnometinib (ATR-002) is a clinical stage, oral MEK inhibitor. It is being evaluated for potential antiviral and immunomodulatory effects in patiuents who are infected by RNA viruses. It has FDA orphan drug designation for hantavirus infections, and clinical studies for influneza (Ph1) and SARS-CoV-2 (Ph2) infections are ongoing. |
| zilucopan |
|
10404 | Zilucoplan is an investigational complement pathway inhibitor with anti-inflammatory potential. It acts as a functional inhibitor of membrane attack complex (MAC) formation. It is being progressed to clinical trial in COVID-19 patients as part of the UK's ACCORD initiative https://bit.ly/2ZXjXOw, to determine if it has efficacy in reducing the hyper-inflammatory response that is a component of severe COVID-19. |
Targets relevant to SARS-CoV-2(COVID-19) - target name links to detailed information in GtoPdb.
| 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. |
| CD147 (basign, HGNC:1116) | 3127 | 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. |
| furin | 2366 | SARS-CoV-2 exploits host furin to activate its spike protein as part of its infection process. Furin inhibitors can block SARS-CoV-2 infection and replication in vitro; Cheng et al. (2020) DOI: 10.1016/j.celrep.2020.108254, bioRxiv preprint PMID: 32869021 |
| GM-CSF | 4942 (ligand) | Analysis of the inflammatory cytokine/chemokine profiles from COVID-19 patients (spanning the spectrum from mild to fatal disease) and archival samples from patients with severe influenza, identified elevated GM-CSF as a principal marker of severe COVID-19 immunopathology (PMID: 33692097, published March 2021). This discovery supports continued targeting of GM-CSF as a therapy for patients with severe COVID-19. Currently the investigational anti-GM-CSF monoclonals lenzilumab, gimsilumab and otilimab are in active COVID-19 clinical trials. |
| Neuropilin 1 | 2998 | Neuropilin 1 (NRP1) has been identified as a host protein with potentiating activity as an entry co-factor for SARS-CoV-2 infection. An anti-NRP1 mAb blocks infection in vitro https://bit.ly/34m2W2B |
| nsp13 (CoV target) | 3261 | Nsp13 (helicase) is a crucial component of the CoV replication machinery, its inhibition is predicted to offer antiviral potential. Nsp13 is also reported to reduce the host interferon response, so limiting this effect would also likely contribute to COVID-19 therapeutic efficacy |
| nsp14 (CoV target) | 3198 | Nsp14 is a bifunctional enzyme. It has methyltransferase (MTase) activity (C-terminal domain), and 3'-to-5' exoribonuclease (ExoN) activity (N-terminal domain). The MTase activity mediates capping of the viral RNA molecules and is essential for viral mRNA stability and translation. Capping helps the virus to evade the host's innate immune response. Based on evidence from SARS-CoV, ExoN function is proposed to provide a proofreading mechanism during genome replication. SAM/SAH derivatives that act as nsp14 inhibitors are being explored for antiviral activity against SARS-CoV-2. |
| nsp15 (CoV target) | 3206 | Nsp15 (NendoU) is a uridylate-specific endoribonuclease that is essential during the coronavirus lifecycle. The search for inhibitors of SARS-CoV-2 nsp15 that may have antiviral action is ongoing. Two allosteric inhibitors have been reported, FUZS-5 (Ligand ID 12200) and LIZA-7 (Ligand ID 12199). The docking positions of these compounds within nsp15 have been determined by X-ray crystallography https://www.biorxiv.org/content/10.1101/2022.09.26.509485v1 |
| OAS1 (HGNC:8086; UniProt: P00973) | n/a | OAS1 is an interferon-induced gene that is part of the innate antiviral defense system within host cells. The protein is an enzyme that generates 2',5'-oligoadenylates (2-5As), and its activity results in the degradation of viral RNAs (via 2-5As-induced activation of RNase L), thus disrupting viral replication. Naturally ocurring variants in human OAS1 have been associated with the risk of developing severe COVID-19/providing a level of protection from SARS-CoV-2 infection PMID: 34336138, PMID: 34402426, PMID: 34557504, PMID: 34282422 (preprint). Prenylated (membrane-bound) splice isoform OAS1 p46 is found in the endomembrane system, where it is able to sense RNA generated by viruses, including SARS-CoV-2, that replicate within intracellular organelles that they appropriate from the host cell's endomembrane system PMID: 34342578. Expression of a prenylated OAS1 isoform was found to be associated with protection from severe COVID-19 in patients. In addition, the SNP Rs10774671 was reported to determine an individual's capacity to generate prenylated OAS1 isoforms. Such OAS1 variants are proposed as inherited genetic elements that can influence the severity of COVID-19 PMID: 34581622 |
| PDE12 | 3207 | PDE12 acts as a negative regulator of a 2-5A (2′,5′-linked oligoadenylate) activated pathway of the innate interferon response to viral infection. PDE12 inhibitors are proposed as novel antiviral agents. Two PDE12-selective inhibitors that were delevoped by Riotech Pharmaceuticals (compounds 63 and 17) have demonstrated antiviral activity against a range of RNA viruses, including SARS-CoV-2, but their chemical structures are yet to be disclosed https://www.biorxiv.org/content/10.1101/2022.09.23.509178v1> |
| SARS-CoV-2 main protease | 3111 | Inhibitors of this viral protease have the potential to block cleavage of nascent viral proteins as they are synthesised in host cells. |
| SARS-CoV-2 nsp3/PL-pro | 3132 | This non-structural CoV protein (a.k.a. papain-like protease, PL-Pro) contains a macrodomain that has been identified as a druggable target (Schuller et al., 2021 DOI: 10.1126/sciadv.abf8711). Viral macrodomains are present primarily in corona, alpha, rubi, and herpes viruses, and they act to circumvent the host innate immune defence mechanism. Small molecule inhibitors that bind to this domain would be expected to compromise the pathogenicity of SARS-CoV-2. |
| 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. |
Useful Publications
Themed Issue: The Pharmacology of COVID-19. Published in November 2020 by the British Journal of Pharmacology.
COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms. Ostaszewski M, Niarakis A, Mazein A, et al. (2021) Mol Syst Biol. 17(10):e10387. https://doi.org/10.15252/msb.202110387 PubMed ID: 34664389
A huge multidisciplinary input to generate an open access, interoperable, computable and constantly evolving resource. Access here https://covid.pages.uni.lu/ & table of contents https://covid.pages.uni.lu/map_contents
Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. Pavors S, et al. (2021) N Engl J Med. Online ahead of print. https://www.nejm.org/doi/10.1056/NEJMoa2109908 PubMed ID: 34379914
Pavord et al. have identified prognostic markers in VITT cases. These may help guide effective treatment options.
Anti-Platelet Drugs Block Platelet Activation by Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Patient Serum. Pairo-Castineira E, Clohisey S, Klaric L, et al. (2021) Blood. Online ahead of print. https://doi.org/10.1182/blood.2021012277 PubMed ID: 34375398
This article clearly identifies a number of drugs that have antithrombotic effects that are worth investigating further as treatments for VITT.
Genes encoding ACE2, TMPRSS2 and related proteins mediating SARS-CoV-2 viral entry are upregulated with age in human cardiomyocytes. Robinson EL et al. (2020) J Mol Cell Cardio. 147:88-91. doi: 10.1016/j.yjmcc.2020.08.009. https://doi.org/10.1126/science.abc6156 PubMed ID: 32818486
This letter explores the expression of genes encoding proteins in the pathways that are involved in SARS-CoV-2 infection in human cardiomyocytes. The authors evaluate the potential of differential expression to contribute towards the vulnerability of older patients to cardiovascular complications such as myocarditis. They discuss the potential of identified proteins (for which clinical drugs already exist), as viable therapeutic targets both during acute infection and during recovery, including offering an opportunity to develop strategies that might improve management of long-term post-infection cardiac symptoms.
Genetic mechanisms of critical illness in Covid-19. Pairo-Castineira E, Clohisey S, Klaric L, et al. (2020) Nature. Online ahead of print. https://doi.org/10.1038/s41586-020-03065-y PubMed ID: 33307546
Discovery of 4 human genetic variants underlying life-threatening illness in COVID-19 - nearest genes are LZTFL1, OAS1, DPP9, TYK2 and IFNAR2.
How does SARS-CoV-2 cause COVID-19?. Matheson NJ and Lehner PJ. (2020) Science. 369(6503):510-511. https://doi.org/10.1126/science.abc6156 PubMed ID: 32732413
A very good summary of the current state of knowledge around SARS-CoV-2 and COVID-19; what we know and what we don't know (yet).
Understanding the age divide in COVID-19: why are children overwhelmingly spared?. Harting MT et al. (2020) Am J Physiol Lung Cell Mol Physiol. 319(1):L39-L44. DOI:10.1152/ajplung.00183.2020. PubMed ID: /32491949
The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing. Xu G et al. (2020) Cell Discovery 6, 73. DOI:10.1038/s41421-020-00225-2.
Establishment and Validation of a Pseudovirus Neutralization Assay for SARS-CoV-2. Nie J et al. (2020) Emerg Microbes Infect. 9(1):680-686. https://doi.org/10.1080/22221751.2020.1743767 PubMed ID: 32207377
In Vitro and Animal Models for SARS-CoV-2 Research. Kazuo Takayama. (2020) Trends Pharmacol Sci. https://doi.org/10.1016/j.tips.2020.05.005 PubMed ID: 32553545
Animal Models for Emerging Coronavirus: Progress and New Insights. Yuan L et al. (2020) Emerg Microbes Infect. 9(1):949-961. https://doi.org/10.1080/22221751.2020.1764871 PubMed ID: 32378471
Current Global Vaccine and Drug Efforts Against COVID-19: Pros and Cons of Bypassing Animal Trials. Deb B et al. (2020) J Biosci. 45(1):82. https://doi.org/10.1007/s12038-020-00053-2 PubMed ID: 32554907
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). Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing [published online ahead of print, 2020 Apr 30]. Nature. 2020;10.1038/s41586-020-2286-9. doi:10.1038/s41586-020-2286-9. PubMed ID: 32353859
Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Grifoni et al. 2020. Cell. DOI:10.1016/j.cell.2020.05.015. Published May 14, 2020
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
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Walls AC et al. (2020) Cell [Online ahead of print]. PubMed ID: 32155444
Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Jin Z et al. (2020) Nature. https://doi.org/10.1038/s41586-020-2223-y
Other Useful Resources
Additional Reading / Blogs
How the coronavirus infects cells — and why Delta is so dangerous. Scudellari M. Nature 595, 640-644 (2021). A in-depth review of the current understanding of the SARS-CoV-2 lifecycle, describing how the virus interacts with host cells/proteins and modulates the host response to maximise its survival
We published a brief update on coronaviruses in February on our blog.
Dr. Chris Southan's blog: Opening up COVID-19 medicinal chemistry (updated 13th August 2020)
Dr. Chris Southan's blog: We predicteth too much, methinks (updated 12th August 2020)
In the Pipeline by Derek Lowe: Good News on the Human Immune Response to the Coronavirus (15th May 2020). Explains the significance of this Cell CD4+ T cell paper
Drug & Vaccine tracker by BioRENDER (updated every Monday)
IUPHAR
The IUPHAR Coronavirus News page contains IUPHAR's official response to COVID-19, as well links to many important pharmacology resources.
Read the statement from the IUPHAR Clinical Division in Response to the COVID-19 Pandemic.
British Pharmacological Society
The British Pharmacological Society COVID-19 Hub provides very useful links and resources for the community. This includes a specific page on trusted resources and information, which includes info on research hubs, journals and publications.
World Health Organisation
WHO: WHO Therapeutics and COVID-19: living guideline - A web resource from the WHO that provides up-to-date recommendations for the use of therapeutics in the treatment of COVID-19. Importantly it also contains comments on therapuetics that are NOT recommended for use in COVID-19 patients.
WHO: Global research on coronavirus disease (COVID-19)
British Society for Immunology
The British Society for Immunology provides an excellent "Connect on Coronavirus" information hub with updates and resources for the immunology community during the Coronavirus outbreak
Connect on Coronavirus: resources provides a useful set of key resources
British Medical Journal
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
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
- ACE inhibitors as a potential risk factor for fatal COVID-19 https://www.bmj.com/content/368/bmj.m810/rr-2
- ACE inhibitors and ARBs are not a risk factor for fatal COVID-19 https://www.bmj.com/content/368/bmj.m810/rr-16
- Are natural ACE inhibitors of interest? https://www.bmj.com/content/368/bmj.m810/rr-17
Latest Coronavirus (COVID-19) research information from NIH: https://www.nih.gov/health-information/coronavirus
Biocentury article: New vaccines and other therapeutics against COVID-19 that are in development- lists compiled by Biocentury and updated daily.
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
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
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
European Bioinformatics Institute (EBI)
EMBL-EBI COVID-19 Data Portal - enables the sharing and analysis of data related to the new coronavirus, SARS-CoV-2. The initiative aims to facilitate international collaboration to accelerate scientific discovery, monitor the pandemic and help develop treatments and a vaccine for the new coronavirus.
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/
