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A Warhead Substitution Study on the Coronavirus Main Protease Inhibitor Nirmatrelvir.

ABSTRACT: The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections.

SUBMITTER: Vankadara S

PROVIDER: S-EPMC9331150 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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A Warhead Substitution Study on the Coronavirus Main Protease Inhibitor Nirmatrelvir.

Vankadara Subramanyam S Dawson Monique Danielle MD Fong Jia Yi JY Oh Qin Yao QY Ang Qi An QA Liu Boping B Chang Hong Yun HY Koh Judice J Koh Xiaoying X Tan Qian Wen QW Joy Joma J Chia Cheng San Brian CSB

ACS medicinal chemistry letters 20220719 8

The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antivi ...[more]

PMID: 35971455

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