An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19)

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.

Keywords:

• Coronavirus
• COVID-19
• Dexamethasone
• Remdesivir
• RNA polymerase

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.

Additional information

Funding

This manuscript was not funded.