Potency, Safety, and Pharmacokinetic Profiles of Potential Inhibitors Targeting SARS-CoV-2 Main Protease

Hylemariam Mihiretie Mengist; Daniel Mekonnen; Ahmed Mohammed; Ronghua Shi; Tengchuan Jin

doi:10.3389/fphar.2020.630500

Potency, Safety, and Pharmacokinetic Profiles of Potential Inhibitors Targeting SARS-CoV-2 Main Protease

Front Pharmacol. 2021 Feb 1:11:630500. doi: 10.3389/fphar.2020.630500. eCollection 2020.

Authors

Hylemariam Mihiretie Mengist^{1

2

3}, Daniel Mekonnen^{2

4}, Ahmed Mohammed², Ronghua Shi², Tengchuan Jin^{1

2

5}

Affiliations

¹ Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
² Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, China.
³ Department of Medical Laboratory Science, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia.
⁴ Department of Medical Laboratory Science, College of Health Science and Medicine, Bahir Dar University, Bahir Dar, Ethiopia.
⁵ CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Science, Shanghai, China.

Abstract

Effective, safe, and pharmacokinetically suitable drugs are urgently needed to curb the ongoing COVID-19 pandemic. The main protease or 3C-like protease (M^pro or 3CL^pro) of SARS-CoV-2 is considered an important target to formulate potent drugs corresponding to its crucial role in virus replication and maturation in addition to its relatively conserved active site. Promising baseline data on the potency and safety of drugs targeting SARS-CoV-2 M^pro are currently available. However, preclinical and clinical data on the pharmacokinetic profiles of these drugs are very limited. This review discusses the potency, safety, and pharmacokinetic profiles of potential inhibitors of SARS-CoV-2 M^pro and forward directions on the development of future studies focusing on COVID-19 therapeutics.

Keywords: COVID-19; SARS-CoV-2; inhibitors; main protease; pharmacokinetics; potency; safety.

Publication types

Review