Potential 3-chymotrypsin-like Cysteine Protease Cleavage Sites in the Coronavirus Polyproteins Pp1a and Pp1ab and Their Possible Relevance to COVID-19 Vaccine and Drug Development

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2021 Apr 29

PMID 33913206

Citations 17

Authors

Shaomin Yan

Guang Wu

Affiliations

Soon will be listed here.

Abstract

Coronavirus (CoV) 3-chymotrypsin (C)-like cysteine protease (3CL ) is a target for anti-CoV drug development and drug repurposing because along with papain-like protease, it cleaves CoV-encoded polyproteins (pp1a and pp1ab) into nonstructural proteins (nsps) for viral replication. However, the cleavage sites of 3CL and their relevant nsps remain unclear, which is the subject of this perspective. Here, we address the subject from three standpoints. First, we explore the inconsistency in the cleavage sites and relevant nsps across CoVs, and investigate the function of nsp11. Second, we consider the nsp16 mRNA overlapping of the spike protein mRNA, and analyze the effect of this overlapping on mRNA vaccines. Finally, we study nsp12, whose existence depends on ribosomal frameshifting, and investigate whether 3CL requires a large number of inhibitors to achieve full inhibition. This perspective helps us to clarify viral replication and is useful for developing anti-CoV drugs with 3CL as a target in the current coronavirus disease 2019 (COVID-19) pandemic.

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