COVID-19 drug repurposing research
Drug repositioning (also known as drug repurposing, re-profiling, re-tasking, or therapeutic switching) is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed.[1] This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments.[2][3][4] Other research directions include the development of a COVID-19 vaccine[5] and convalescent plasma transfusion.[6]
This article is about drugs that may be repurposed for treating COVID-19. For COVID-19 vaccines, see COVID-19 vaccine. For potential therapeutic drugs for COVID-19, see COVID-19 drug development.
Several existing antiviral medications, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV/AIDS, and malaria, have been researched as potential COVID-19 treatments, with some moving into clinical trials.[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]
Background[edit]
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.[10] Since the process of developing and licensing a new drug for COVID-19 was expected to pose a particularly long delay, researchers have been probing the existing compendium of approved antivirals and other drugs as a cost-effective strategy in the meantime.[3][10] In early 2020 hundreds of hospitals and universities began their own trials of existing safe drugs with repurposing potential against COVID-19.[11]
Drug repurposing usually requires three steps before taking the drug across the development pipeline: recognition of the right drug; systematic evaluation of the drug effect in clinical models; and estimation of usefulness in phase II clinical trials.[12]
One approach used in repositioning is to look for drugs that act through virus-related targets such as the RNA genome (i.e. remdesivir). Another approach concerns drugs acting through polypeptide packing (i.e. lopinavir).[10]
The rush to publish papers about the pandemic resulted in some scandals of inaccurate scientific publications.[13] Some early studies reporting the efficacy of hydroxychloroquine and remdesivir convinced drug agencies such as Food and Drug Administration (FDA) and European Medicines Agency to approve the off-label use by issuing Emergency Use Authorizations which were later revoked as new evidence showed these drugs have no effect on the course of COVID-19.[14] These false-positive results can be explained in terms of the base-rate fallacy and the rapid changes in clinical guidance regarding COVID-19 treatment could have been avoided if mechanistic evidence for and against repurposing candidates were carefully assessed[15] and the standard evidence amalgamation tools such as meta-analysis were routinely applied.[16]
Anticoagulants[edit]
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).[27] Several anticoagulants have been tested in Italy, with low-molecular-weight heparin being widely used to treat patients, prompting the Italian Medicines Agency to publish guidelines on its use.[28][29]
Scientists have identified an ability of heparin to bind to the spike protein of the SARS-CoV-2 virus, neutralising it, and proposed the drug as a possible antiviral.[30]
A multicenter study on 300 patients researching the use of enoxaparin sodium at prophylaxis and therapeutic dosages was announced in Italy on 14 April.[31]
The anticoagulant dipyridamole is proposed as a treatment for COVID-19,[32] and a clinical trial is underway.[33]
Antioxidants[edit]
Acetylcysteine (NAC)[edit]
Acetylcysteine is being considered as a possible treatment for COVID-19.[44]
Interferons[edit]
Drugs with immune modulating effects that may prove useful in COVID-19 treatment include type I Interferons such as Interferon-β, peginterferon alpha-2a and -2b.[158][159]
IFN-β 1b have been shown in an open label randomised controlled trial in combination with lopinavir/ ritonavir and ribavirin to significantly reduce viral load, alleviate symptoms and reduce cytokine responses when compared to lopinavir/ ritonavir alone.<Lancet 2020;395(10238):1695-1704> IFN-β will be included in the international Solidarity Trial in combination with the HIV drugs Lopinavir and Ritonavir.[158] as well as the REMAP-CAP[159] Finnish biotech firm Faron Pharmaceuticals continues to develop INF-beta for ARDS and is involved in worldwide initiatives against COVID-19, including the Solidarity trial.[160] UK biotech firm Synairgen started conducting trials on IFN-β, a drug that was originally developed to treat COPD.[135]
Minerals[edit]
Zinc[edit]
The National Institutes of Health (NIH) COVID-19 Treatment Guidelines states "there is insufficient evidence to recommend either for or against the use of zinc for the treatment of COVID-19" and that "the Panel recommends against using zinc supplementation above the recommended dietary allowance for the prevention of COVID-19, except in a clinical trial (BIII)."[208]
Found ineffective[edit]
The use of aspirin, hydroxychloroquine,[230] azithromycin,[231] and colchicine were found ineffective against COVID-19.[232] The use of the combination of lopinavir and ritonavir together was found ineffective against COVID-19.[136][232] The use of the combination of etesevimab and bamlanivimab together was found ineffective against the Omicron variant.[232]