New Perspectives on Antimicrobial Agents: Remdesivir Treatment for COVID-19

Abstract

Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is the prodrug of an adenosine analogue that inhibits viral replication of several RNA virus families, including Coronaviridae Preclinical data in animal models of coronavirus diseases, including COVID-19, have demonstrated that early treatment with remdesivir leads to improved survival, decreased lung injury, and decreased levels of viral RNA. Recent clinical data have demonstrated the clinical activity of remdesivir in terms of faster time to recovery in patients with severe COVID-19 and higher odds of improved clinical status in patients with moderate COVID-19. Here, clinical trials published to date are presented and appraised. Remdesivir's potential benefits and its favorable adverse-event profile make it an option for the treatment of COVID-19. This article examines the available literature describing remdesivir's pharmacology, pharmacokinetics, and preclinical and clinical data.

Keywords: COVID-19; SARS-CoV-2; antiviral; remdesivir.

FIG 1

Chemical structure of remdesivir and its metabolites (adapted from reference 12).

FIG 2

Mechanism of remdesivir. (Step 1) Entry of SARS-CoV-2 into the target cell by binding to the ACE-2 receptor on the cell surface. (Step 2) Once SARS-CoV-2 enters the cell, it releases its viral RNA. (Step 3) SARS-CoV-2 uses the host machinery to translate RNA into RNA-dependent RNA polymerase (RdRp). (Step 4) RdRp is then used to facilitate viral replication. (Step 5) Once remdesivir enters the cell, it is converted into remdesivir triphosphate, which competes with endogenous ATP, which is used as a source of nucleotide, for incorporation into RdRp, leading to chain termination. (Courtesy of Lama Albadi, reproduced with permission.)