A head-to-head comparison of the inhibitory activities of 15 peptidomimetic SARS-CoV-2 3CLpro inhibitors

Bioorganic & Medicinal Chemistry Letters
2021.0

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has created an unprecedented global health emergency. As of July 2021, only three antiviral therapies have been approved by the FDA for treating infected patients, highlighting the urgent need for more antiviral drugs. The SARS-CoV-2 3CL protease (3CLpro) is deemed an attractive drug target due to its essential role in viral polyprotein processing and pathogenesis. Indeed, a number of peptidomimetic 3CLpro inhibitors armed with electrophilic warheads have been reported by various research groups that can potentially be developed for treating COVID-19. However, it is currently impossible to compare their relative potencies due to the different assays employed. To solve this, we conducted a head-to-head comparison of fifteen reported peptidomimetic inhibitors in a standard FRET-based SARS-CoV-2 3CLpro inhibition assay to compare and identify potent inhibitors for development. Inhibitor design and the suitability of various warheads are also discussed.

Knowledge Graph

Similar Paper

A head-to-head comparison of the inhibitory activities of 15 peptidomimetic SARS-CoV-2 3CLpro inhibitors
Bioorganic & Medicinal Chemistry Letters 2021.0
An Overview of Severe Acute Respiratory Syndrome–Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy
Journal of Medicinal Chemistry 2016.0
Discovery of 9,10-dihydrophenanthrene derivatives as SARS-CoV-2 3CLpro inhibitors for treating COVID-19
European Journal of Medicinal Chemistry 2022.0
Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors
Bioorganic & Medicinal Chemistry 2021.0
Progress and Challenges in Targeting the SARS-CoV-2 Papain-like Protease
Journal of Medicinal Chemistry 2022.0
Structure-Based Design of a Dual-Targeted Covalent Inhibitor Against Papain-like and Main Proteases of SARS-CoV-2
Journal of Medicinal Chemistry 2022.0
A review of the latest research on M<sup>pro</sup> targeting SARS-COV inhibitors
RSC Medicinal Chemistry 2021.0
Targeting SARS-CoV-2 Main Protease for Treatment of COVID-19: Covalent Inhibitors Structure–Activity Relationship Insights and Evolution Perspectives
Journal of Medicinal Chemistry 2022.0
Discovery of 2-(furan-2-ylmethylene)hydrazine-1-carbothioamide derivatives as novel inhibitors of SARS-CoV-2 main protease
European Journal of Medicinal Chemistry 2022.0
High-Throughput Screening for Inhibitors of the SARS-CoV-2 Protease Using a FRET-Biosensor
Molecules 2020.0