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Editorials

Remdesivir in covid-19

BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1610 (Published 22 April 2020) Cite this as: BMJ 2020;369:m1610

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  1. Robin E Ferner, honorary professor of clinical pharmacology1,
  2. Jeffrey K Aronson, clinical pharmacologist2
  1. 1Institute of Clinical Sciences, University of Birmingham, Birmingham, UK
  2. 2Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  1. Correspondence to: R E Ferner r.e.ferner{at}bham.ac.uk

A drug with potential—don’t waste time on uncontrolled observations

The recent publication of an industry sponsored, open, non-randomised study of remdesivir in a heterogeneous patient population has added to the confusion surrounding the drug treatment of covid-19.1

The SARS-CoV-2 virus that causes covid-19 has potential therapeutic targets similar to those of other RNA coronaviruses such as SARS-CoV-1, which causes severe acute respiratory syndrome (SARS), and MERS-CoV, the cause of Middle East respiratory syndrome.

Coronaviruses enter host cells by binding to and fusing with cell membranes. Once inside, they subvert the host cell’s machinery to replicate, using the virus’s RNA dependent RNA polymerase (RdRp).2 This non-structural protein is highly conserved among different strains, making it a potentially attractive drug target. The principle of using synthetic analogues of nucleosides and nucleotides to inhibit RdRp has led, for example, to sofosbuvir, a successful treatment for hepatitis C infection.3

Remdesivir is a pro drug. Its active analogue enters and accumulates in cells, inhibiting viral RdRp4 and stopping viral replication. Coronaviruses have a “proofreading” enzyme (exoribonuclease) that corrects errors in the RNA sequence, potentially limiting the effects of analogues,56 but …

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