Abstract
Introduction
Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment.
Areas covered
In this review, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction.
Expert opinion
RDV is the most widely investigated antiviral drug for the treatment of COVID-19. This attention on RDV activity against SARS-CoV-2 is justified by promising in vitro studies, which demonstrated that RDV was able to suppress viral replication without significant toxicity. Such activity was confirmed by an investigation in an animal model and by the results of preliminary clinical investigations. Nevertheless, the efficacy of RDV in reducing mortality has not been clearly demonstrated.
Abbreviations
COVID-19: coronavirus disease 19
RDV: Remdesivir
RdRp: RNA-dependent RNA polymerase
HIV: Human Immunodeficiency Virus
HCV: Hepatitis C Virus
EBOV: Ebola virus
SARS-CoV: Severe Acute Respiratory Syndrome
MERS: Middle East Respiratory Syndrome
BatCoV: bat coronavirus
WHO: World Health Organization
ARDS: acute respiratory distress syndrome
CDC: Centers for Disease Control and Prevention
NUC: 1′-cyano-substituted adenine C-nucleoside ribose analogue
CN: carbon-nitrogen
qRT-PCR: quantitative real-time RT-PCR
NP: virus nucleoprotein
RTP: triphosphate form
RMP: monophosphate form
RT: nucleotide form
CES1: carboxylesterase 1
PKs: pharmacokinetics
EMA: European Medicines Agency
MRP4: multidrug resistance-associated protein 4
FDA: Food and Drug Administration
Declaration of Interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.