Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities

J Med Chem. 2020 Nov 12;63(21):12256-12274. doi: 10.1021/acs.jmedchem.0c00502. Epub 2020 Jun 25.

Abstract

Recently, a novel coronavirus initially designated 2019-nCoV but now termed SARS-CoV-2 has emerged and raised global concerns due to its virulence. SARS-CoV-2 is the etiological agent of "coronavirus disease 2019", abbreviated to COVID-19, which despite only being identified at the very end of 2019, has now been classified as a pandemic by the World Health Organization (WHO). At this time, no specific prophylactic or postexposure therapy for COVID-19 are currently available. Viral entry is the first step in the SARS-CoV-2 lifecycle and is mediated by the trimeric spike protein. Being the first stage in infection, entry of SARS-CoV-2 into host cells is an extremely attractive therapeutic intervention point. Within this review, we highlight therapeutic intervention strategies for anti-SARS-CoV, MERS-CoV, and other coronaviruses and speculate upon future directions for SARS-CoV-2 entry inhibitor designs.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Antiviral Agents / therapeutic use*
  • COVID-19 / prevention & control
  • COVID-19 Drug Treatment*
  • Cathepsin L / antagonists & inhibitors
  • Cell Line
  • Humans
  • Protein Domains
  • SARS-CoV-2 / drug effects*
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors
  • Virus Internalization / drug effects*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antiviral Agents
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Angiotensin-Converting Enzyme 2
  • CTSL protein, human
  • Cathepsin L