Recent Drug Development and Medicinal Chemistry Approaches for the Treatment of SARS-CoV-2 Infection and COVID-19

Arun K Ghosh; Jennifer L Mishevich; Andrew Mesecar; Hiroaki Mitsuya

doi:10.1002/cmdc.202200440

Recent Drug Development and Medicinal Chemistry Approaches for the Treatment of SARS-CoV-2 Infection and COVID-19

ChemMedChem. 2022 Nov 18;17(22):e202200440. doi: 10.1002/cmdc.202200440. Epub 2022 Oct 13.

Authors

Arun K Ghosh^{1

2}, Jennifer L Mishevich^{1

2}, Andrew Mesecar^{1

3

4}, Hiroaki Mitsuya^{5

6

7}

Affiliations

¹ Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
² Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
³ Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.
⁴ Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA.
⁵ Departments of Hematology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan.
⁶ Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD, 20892, USA.
⁷ National Center for Global Health and Medicine Research Institute, Shinjuku, Tokyo, 162-8655, Japan.

Abstract

COVID-19, caused by SARS-CoV-2 infection, continues to be a major public health crisis around the globe. Development of vaccines and the first cluster of antiviral drugs has brought promise and hope for prevention and treatment of severe coronavirus disease. However, continued development of newer, safer, and more effective antiviral drugs are critically important to combat COVID-19 and counter the looming pathogenic variants. Studies of the coronavirus life cycle revealed several important biochemical targets for drug development. In the present review, we focus on recent drug design and medicinal chemistry efforts in small molecule drug discovery, including the development of nirmatrelvir that targets viral protein synthesis and remdesivir and molnupiravir that target viral RdRp. These are recent FDA approved drugs for the treatment of COVID-19.

Keywords: COVID-19; SARS-CoV-2; antiviral drugs; coronavirus; drug design; inhibitors; protein X-ray structures.

Publication types

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

MeSH terms

Antiviral Agents / chemistry
Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use
COVID-19 Drug Treatment*
Chemistry, Pharmaceutical
Drug Development
Humans
SARS-CoV-2

Substances

Antiviral Agents

Grants and funding

R01 AI158649/AI/NIAID NIH HHS/United States