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Targeting SARS-CoV-2 papain-like protease in the postvaccine era.

ABSTRACT: While vaccines remain at the forefront of global healthcare responses, pioneering therapeutics against SARS-CoV-2 are expected to fill the gaps for waning immunity. Rapid development and approval of orally available direct-acting antivirals targeting crucial SARS-CoV-2 proteins marked the beginning of the era of small-molecule drugs for COVID-19. In that regard, the papain-like protease (PLpro) can be considered a major SARS-CoV-2 therapeutic target due to its dual biological role in suppressing host innate immune responses and in ensuring viral replication. Here, we summarize the challenges of targeting PLpro and innovative early-stage PLpro-specific small molecules. We propose that state-of-the-art computer-aided drug design (CADD) methodologies will play a critical role in the discovery of PLpro compounds as a novel class of COVID-19 drugs.

SUBMITTER: Ton AT

PROVIDER: S-EPMC9399131 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Targeting SARS-CoV-2 papain-like protease in the postvaccine era.

Ton Anh-Tien AT Pandey Mohit M Smith Jason R JR Ban Fuqiang F Fernandez Michael M Cherkasov Artem A

Trends in pharmacological sciences 20220824 11

While vaccines remain at the forefront of global healthcare responses, pioneering therapeutics against SARS-CoV-2 are expected to fill the gaps for waning immunity. Rapid development and approval of orally available direct-acting antivirals targeting crucial SARS-CoV-2 proteins marked the beginning of the era of small-molecule drugs for COVID-19. In that regard, the papain-like protease (PLpro) can be considered a major SARS-CoV-2 therapeutic target due to its dual biological role in suppressing ...[more]

PMID: 36114026

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