High-throughput design of symmetrical dimeric SARS-CoV-2 main protease: structural and physical insights into hotspots for adaptation and therapeutics.
Phys Chem Chem Phys
; 24(16): 9141-9145, 2022 Apr 20.
Article
in English
| MEDLINE | ID: covidwho-1784055
ABSTRACT
Dimerization of SARS-CoV-2 main protease (Mpro) is a prerequisite for its processing activity. With >2000 mutations already reported in Mpro, SARS-CoV-2 may accumulate mutations in the Mpro dimeric interface to stabilize it further. We employed high-throughput protein design strategies to design the symmetrical dimeric interface of Mpro (300 000 designs) to identify mutational hotspots that render the Mpro more stable. We found that â¼22% of designed mutations that yield stable Mpro dimers already exist in SARS-CoV-2 genomes and are currently circulating. Our multi-parametric analyses highlight potential Mpro mutations that SARS-CoV-2 may develop, providing a foundation for assessing viral adaptation and mutational surveillance.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protein Engineering
/
Coronavirus 3C Proteases
/
SARS-CoV-2
Limits:
Humans
Language:
English
Journal:
Phys Chem Chem Phys
Journal subject:
Biophysics
/
Chemistry
Year:
2022
Document Type:
Article
Affiliation country:
D2cp00171c
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