Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery

Curr Top Med Chem. 2020;20(16):1423-1433. doi: 10.2174/1568026620999200517043137.

Abstract

Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARS-CoV-2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit the spread of SARS-CoV-2 and morbidity and mortality due to the COVID-19 pandemic.

Keywords: 3Clpro; COVID-19; Camostat; Coronavirus SARS-CoV-2; RNA polymerase; Remdesivir; S protein; α-Ketoamides.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Antiviral Agents / therapeutic use*
  • Betacoronavirus / drug effects*
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus 3C Proteases
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • Coronavirus RNA-Dependent RNA Polymerase
  • Cysteine Endopeptidases
  • Drug Repositioning*
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A / chemistry
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Virus Internalization*
  • Virus Replication*

Substances

  • Antiviral Agents
  • Spike Glycoprotein, Coronavirus
  • Viral Nonstructural Proteins
  • spike protein, SARS-CoV-2
  • Coronavirus RNA-Dependent RNA Polymerase
  • NSP12 protein, SARS-CoV-2
  • RNA-Dependent RNA Polymerase
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases