COVID-19 drug repurposing research
[7][8][9] In a statement to the journal Nature Biotechnology in February 2020, US National Institutes of Health Viral Ecology Unit chief Vincent Munster said, "The general genomic layout and the general replication kinetics and the biology of the MERS, SARS and [SARS-CoV-2] viruses are very similar, so testing drugs which target relatively generic parts of these coronaviruses is a logical step".
[2] Outbreaks of novel emerging infections such as COVID-19 pose unique challenges to discover treatments appropriate for clinical use, given the small amount of time available for drug discovery.
[21] In January 2021, the UK National Health Service issued guidance that the immune modulating drugs tocilizumab and sarilumab were beneficial when given promptly to people with COVID-19 admitted to intensive care, following research which found a reduction in the risk of death by 24%.
[24] Medications to prevent blood clotting have been suggested for treatment, and anticoagulant therapy with low-molecular-weight heparin appears to be associated with better outcomes in severe COVID-19 showing signs of coagulopathy (elevated D-dimer).
[35][36] The potential mechanisms how fluvoxamine and fluoxetin are contributing to prevent the development of severe respiratory symptoms of COVID-19 by protecting the type 2 lung alveolar cells have been summarized in a review in March 2022.
[38][39][40] On 16 December, the NIH found that use of fluvoxamine did not impact incidence of covid-related hospitalizations and considered the evidence insufficient to recommend either for or against the drug.
[41] On 23 December, under very low certainty evidence, the Ontario clinical practice guideline suggested considering the drug to treat mildly ill patients within 7 days of symptom onset.
[65] Several countries initially used chloroquine or hydroxychloroquine for treatment of persons hospitalized with COVID-19 (as of March 2020), though the drug was not formally approved through clinical trials.
[69] On 24 April 2020, citing the risk of "serious heart rhythm problems", the FDA posted a caution against using the drug for COVID-19 "outside of the hospital setting or a clinical trial".
[71][72] On 15 June 2020, the FDA revoked its emergency use authorization, stating that it was "no longer reasonable to believe" that the drug was effective against COVID-19 or that its benefits outweighed "known and potential risks".
[77] The World Health Organization (WHO),[78] the European Medicines Agency (EMA),[79] the United States Food and Drug Administration (FDA),[80] and the Infectious Diseases Society of America (IDSA)[81] all advise against using ivermectin in an attempt to treat or prevent COVID-19.
[95] A preprint published in July 2020, reported that pyronaridine and artesunate exhibit antiviral activity against SARS-CoV-2 and influenza viruses using human lung epithelial (Calu-3) cells.
[106][107] A clinical trial, which has not as of 1 October 2021 been peer reviewed, suggests molnupiravir taken orally can reduce the risk of hospitalization and prevent death in patients diagnosed with COVID-19.
[117][90] There is limited evidence suggesting that, compared to other antiviral drugs, favipiravir might improve outcomes for people with COVID-19, but more rigorous studies are needed before any conclusions can be drawn.
[123] On 30 May 2020, the Russian Health Ministry approved a generic version of favipiravir named Avifavir, which proved highly effective in the first phase of clinical trials.
[124][125][126] In June 2020, India approved the use of a generic version of favipravir called FabiFlu, developed by Glenmark Pharmaceuticals, in the treatment of mild to moderate cases of COVID-19.
[130] Protease inhibitors approved for treating human immunodeficiency viruses (HIV) – lopinavir and ritonavir – have preliminary evidence of activity against the coronaviruses, SARS and MERS.
[136] On 29 June, the chief investigators of the UK RECOVERY Trial reported that there was no clinical benefit from use of lopinavir-ritonavir in 1,596 people hospitalized with severe COVID-19 infection over 28 days of treatment.
[137][138] A study published in October 2020, screening those drugs approved by the US Food and Drug Administration (FDA) which target SARS-CoV-2 spike (S) protein proposed that the current unbalanced combination formula of lopinavir might in fact interfere with the ritonavir's blocking activity on the receptor binding domain-human angiotensin converting enzyme-2 (RBD-hACE2) interaction, thus effectively limiting its therapeutic benefit in COVID-19 cases.
[139] In 2022, the PANORAMIC trial is testing the effectiveness of nirmatrelvir combined with ritonavir, and molnupiravir in preventing hospitalization and helping faster recovery for people aged over 50 and those at higher risk due to underlying health conditions.
Remdesivir, sold under the brand name Veklury,[143][144] is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences.
[151] Remdesivir is a prodrug that is intended to allow intracellular delivery of GS-441524 monophosphate and subsequent biotransformation into GS-441524 triphosphate, a ribonucleotide analogue inhibitor of viral RNA polymerase.
[155] In December 2021, anakinra (Kineret) was authorized in the European Union for the treatment of COVID-19 in adults with pneumonia requiring supplemental oxygen (low or high flow oxygen) and who are at risk of developing severe respiratory failure, as determined by blood levels of a protein called suPAR (soluble urokinase plasminogen activator receptor) of at least 6 ng per ml.
[167] A multi-center, randomized controlled trial of dexamethasone in treating acute respiratory distress syndrome (ARDS), published in February 2020, showed reduced need for mechanical ventilation and mortality.
[180] In September 2020, the European Medicines Agency (EMA) endorsed the use of dexamethasone in adults and adolescents (from twelve years of age and weighing at least 40 kilograms (88 lb)) who require supplemental oxygen therapy.
[182] In September 2020, a meta-analysis published by the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group found hydrocortisone to be effective in reducing mortality rate of critically ill COVID-19 patients when compared to other usual care or a placebo.
[183] The use of corticosteroids can cause a severe and deadly "hyperinfection" syndrome for people with strongyloidiasis, which may be an underlying condition in populations exposed to the parasite Strongyloides stercoralis.
"[191] In an update posted December 2022, the NIH position was unchanged: Three meta-analyses of people hospitalized with severe COVID-19 - with a high overlap in the clinical trials being included - reported a significant reduction in the risk of all-cause, in-hospital mortality with the administration of vitamin C relative to no vitamin C. There were no significant differences in ventilation incidence, hospitalization duration or length of intensive care unit stay between the two groups.
[203][204][196][205] The effects of oral vitamin D supplementation on the need for intensive care unit (ICU) admission and mortality in hospitalized COVID-19 patients has been the subject of a meta-analysis.
[206] The certainty of these analyses is limited by the heterogenicity in the studies which include both vitamin D3 (cholecalciferol) and calcifediol, but these findings indicate a potential role in improving COVID-19 severity, with more robust data being required to substantiate any effects on mortality.
