Insights into SARS-CoV-2: Medicinal Chemistry Approaches to Combat Its Structural and Functional Biology

Top Curr Chem (Cham). 2021 Apr 22;379(3):23. doi: 10.1007/s41061-021-00335-9.

Abstract

Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still a pandemic around the world. Currently, specific antiviral drugs to control the epidemic remain deficient. Understanding the details of SARS-CoV-2 structural biology is extremely important for development of antiviral agents that will enable regulation of its life cycle. This review focuses on the structural biology and medicinal chemistry of various key proteins (Spike, ACE2, TMPRSS2, RdRp and Mpro) in the life cycle of SARS-CoV-2, as well as their inhibitors/drug candidates. Representative broad-spectrum antiviral drugs, especially those against the homologous virus SARS-CoV, are summarized with the expectation they will drive the development of effective, broad-spectrum inhibitors against coronaviruses. We are hopeful that this review will be a useful aid for discovery of novel, potent anti-SARS-CoV-2 drugs with excellent therapeutic results in the near future.

Keywords: Antiviral; COVID-19; Drug discovery; SARS-CoV-2; Structural biology.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / antagonists & inhibitors
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antiviral Agents / chemistry*
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • COVID-19 / pathology
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Drug Repositioning
  • Humans
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Matrix Proteins / chemistry*
  • Viral Matrix Proteins / metabolism
  • Virus Internalization / drug effects

Substances

  • Antiviral Agents
  • Spike Glycoprotein, Coronavirus
  • Viral Matrix Proteins
  • membrane protein, SARS-CoV-2
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human