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Review
. 2020 Oct 14;34(1):e00162-20.
doi: 10.1128/CMR.00162-20. Print 2020 Dec 16.

Remdesivir against COVID-19 and Other Viral Diseases

Jakob J Malin  1   2 , Isabelle Suárez  3   4 , Vanessa Priesner  3 , Gerd Fätkenheuer  3 , Jan Rybniker  3   2   4
Affiliations
Review

Remdesivir against COVID-19 and Other Viral Diseases

Jakob J Malin et al. Clin Microbiol Rev. .

Abstract

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.

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

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Figures

FIG 1
FIG 1
Milestones in the discovery of remdesivir as an anti-COVID-19 treatment. Shown is a chronological summary of important achievements in the discovery and preclinical and clinical evaluations of remdesivir (GS-5734). Achievements appear according to the year of manuscript publication or reception at a peer-reviewed journal. COVID-19, coronavirus disease 2019; EBOV, ebolavirus; EMA, European Medicines Agency; EVD, ebolavirus disease; MERS-CoV, Middle East respiratory syndrome coronavirus; SARS-CoV(-2), severe acute respiratory distress syndrome coronavirus (2); RCT, randomized controlled clinical trial; mAB, monoclonal antibody. (See references , , , , and .)
FIG 2
FIG 2
Intracellular activation of remdesivir (GS-5734) and inhibition of coronavirus replication. Passage through the cell membrane by remdesivir is facilitated by the prodrug component attached to the nucleoside core. Upon entering the target cell, the pronucleotide undergoes further phosphorylation steps to become the active triphosphate metabolite that effectively inhibits viral RNA replication. Delayed chain termination is caused by the following processes: (i) misintegration of nucleoside triphosphate (NTP) into replicating RNA by RdRp, (ii) prevention of further chain elongation after NTP plus 3 additional nucleosides, and (iii) premature termination of RNA synthesis.
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