Drug Development and Medicinal Chemistry Efforts toward SARS-Coronavirus and Covid-19 Therapeutics

ChemMedChem. 2020 Jun 4;15(11):907-932. doi: 10.1002/cmdc.202000223. Epub 2020 May 7.


The COVID-19 pandemic caused by SARS-CoV-2 infection is spreading at an alarming rate and has created an unprecedented health emergency around the globe. There is no effective vaccine or approved drug treatment against COVID-19 and other pathogenic coronaviruses. The development of antiviral agents is an urgent priority. Biochemical events critical to the coronavirus replication cycle provided a number of attractive targets for drug development. These include, spike protein for binding to host cell-surface receptors, proteolytic enzymes that are essential for processing polyproteins into mature viruses, and RNA-dependent RNA polymerase for RNA replication. There has been a lot of ground work for drug discovery and development against these targets. Also, high-throughput screening efforts have led to the identification of diverse lead structures, including natural product-derived molecules. This review highlights past and present drug discovery and medicinal-chemistry approaches against SARS-CoV, MERS-CoV and COVID-19 targets. The review hopes to stimulate further research and will be a useful guide to the development of effective therapies against COVID-19 and other pathogenic coronaviruses.

Keywords: Covid-19; SARS-CoV; coronavirus; drug discovery; protease inhibitors.

Publication types

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

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • COVID-19
  • Chemistry, Pharmaceutical / trends*
  • Coronavirus Infections / drug therapy*
  • Drug Development*
  • Drug Discovery
  • Humans
  • Models, Molecular
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Protease Inhibitors / therapeutic use


  • Antiviral Agents
  • Protease Inhibitors