Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV

Chembiochem. 2020 Mar 2;21(5):730-738. doi: 10.1002/cbic.202000047. Epub 2020 Feb 25.

Abstract

With the current trajectory of the 2019-nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better-studied cousin, SARS-CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA-dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS-CoV. Herein, we suggest four potential drug candidates (an ACE2-based peptide, remdesivir, 3CLpro-1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019-nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad-spectrum anti-coronaviral agents for future epidemics.

Keywords: 2019-nCoV; 3CLpro; RdRp; SARS; antiviral agents; coronavirus; spike proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / therapeutic use*
  • Betacoronavirus* / enzymology
  • Betacoronavirus* / genetics
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / prevention & control*
  • Coronavirus Infections / transmission
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • Drug Design
  • Humans
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / prevention & control*
  • Pneumonia, Viral / transmission
  • RNA Replicase / chemistry
  • RNA Replicase / genetics
  • RNA Replicase / metabolism

Substances

  • Antiviral Agents
  • RNA Replicase
  • 3C-like proteinase, Coronavirus
  • Cysteine Endopeptidases

Supplementary concepts

  • COVID-19
  • COVID-19 drug treatment
  • severe acute respiratory syndrome coronavirus 2