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Published on: December 23, 2020
Spatial and temporal roles of SARS-CoV PLpro -A snapshot
1National Engineering Research Center for Non-Food Biorefinery, State Key Laboratory of Non-Food Biomass and Enzyme Technology, Guangxi Biomass Engineering Technology Research Center, Guangxi Key Laboratory of Bio-Refinery, Guangxi Academy of Sciences, Nanning, China.
SARS-CoV papain-like protease (PLpro) plays a dual role in viral replication and host immunity. This review explores how PLpro manages conflicting functions to evade immune responses, offering insights for SARS-CoV-2 infection strategies.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Coronaviruses, including SARS-CoV and SARS-CoV-2, encode structural proteins and polyproteins processed into nonstructural proteins (nsps).
- Papain-like protease (PLpro) is a key viral enzyme involved in polyprotein processing and host immune modulation.
Purpose of the Study:
- To analyze the dual roles of SARS-CoV PLpro in viral replication and innate immunity.
- To elucidate the mechanisms by which PLpro manages contradictory functions.
- To provide insights into potential therapeutic strategies against SARS-CoV-2 infections.
Main Methods:
- Review of existing literature on SARS-CoV PLpro function.
- Analysis of protein-protein interactions involving PLpro, RCHY1, and target substrates.
- Examination of ubiquitination and ISGylation pathways modulated by PLpro.
Main Results:
- PLpro ubiquitination of p53 aids viral replication by preventing p53-mediated inhibition.
- PLpro-mediated ubiquitination/ISGylation of host factors (IκBα, TRAFs, STING) can trigger innate immune responses.
- PLpro interacts with RCHY1 to ubiquitinate target proteins, including p53.
Conclusions:
- SARS-CoV PLpro exhibits a complex role, balancing viral replication needs with immune evasion strategies.
- Understanding PLpro's management of these conflicting functions is crucial for developing effective antiviral therapies.
- This analysis offers a perspective on combating SARS-CoV-2 by targeting viral proteases.
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