Primer for Designing Main Protease (Mpro) Inhibitors of SARS-CoV-2.
J Phys Chem Lett
; 13(25): 5776-5786, 2022 Jun 30.
Article
in English
| MEDLINE | ID: covidwho-1915250
ABSTRACT
The COVID-19 outbreak has been devastating, with hundreds of millions of infections and millions of deaths reported worldwide. In response, the application of structure-activity relationships (SAR) upon experimentally validated inhibitors of SARS-CoV-2 main protease (Mpro) may provide an avenue for the identification of new lead compounds active against COVID-19. Upon the basis of information gleaned from a combination of reported crystal structures and the docking of experimentally validated inhibitors, four "rules" for designing potent Mpro inhibitors have been proposed. The aim here is to guide medicinal chemists toward the most probable hits and to provide guidance on repurposing available structures as Mpro inhibitors. Experimental examination of our own previously reported inhibitors using the four "rules" identified a potential lead compound, the cathepsin inhibitor GB111-NH2, that was 2.3 times more potent than SARS-CoV-2 Mpro inhibitor N3.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Phys Chem Lett
Year:
2022
Document Type:
Article
Affiliation country:
Acs.jpclett.2c01193
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