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.
FASEB J
; 35(5): e21573, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-1207324
ABSTRACT
Coronavirus (CoV) 3-chymotrypsin (C)-like cysteine protease (3CLpro ) 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 3CLpro 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 3CLpro 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 3CLpro as a target in the current coronavirus disease 2019 (COVID-19) pandemic.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Proteins
/
Coronavirus 3C Proteases
/
SARS-CoV-2
Type of study:
Prognostic study
Topics:
Vaccines
Language:
English
Journal:
FASEB J
Journal subject:
Biology
/
Physiology
Year:
2021
Document Type:
Article
Affiliation country:
Fj.202100280RR
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