Analysis of the SARS-CoV-2-host protein interaction network reveals new biology and drug candidates: focus on the spike surface glycoprotein and RNA polymerase

Expert Opin Drug Discov. 2021 Aug;16(8):881-895. doi: 10.1080/17460441.2021.1909566. Epub 2021 Apr 6.

Abstract

Introduction: The COVID-19 pandemic originated from the emergence of anovel coronavirus, SARS-CoV-2, which has been intensively studied since its discovery in order to generate the knowledge necessary to accelerate the development of vaccines and antivirals. Of note, many researchers believe there is great potential in systematically identifying host interactors of viral factors already targeted by existing drugs.Areas Covered: Herein, the authors discuss in detail the only available large-scale systematic study of the SARS-CoV-2-host protein-protein interaction network. More specifically, the authors review the literature on two key SARS-CoV-2 drug targets, the Spike surface glycoprotein, and the RNA polymerase. The authors also provide the reader with their expert opinion and future perspectives.Expert opinion: Interactions made by viral proteins with host factors reveal key functions that are likely usurped by the virus and, as aconsequence, points to known drugs that can be repurposed to fight viral infection and collateral damages that can exacerbate various disease conditions in COVID-19.

Keywords: COVID-19; RNA-dependent RNA polymerase; SARS-CoV-2; SARS-CoV-2-host protein interactome; antiviral drugs discovery; spike protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Drug Development
  • Drug Repositioning
  • Humans
  • Protein Interaction Maps
  • RNA-Dependent RNA Polymerase / metabolism
  • SARS-CoV-2 / drug effects*
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • Antiviral Agents
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • RNA-Dependent RNA Polymerase

Grants and funding

B Coulombe is supported by the Bell-Bombardier Chair of Excellence while E Sokullu is the recipient of a postdoctoral fellowship from the Montreal Clinical Research Institute (IRCM).