Structural basis of main proteases of HCoV-229E bound to inhibitor PF-07304814 and PF-07321332.
Biochem Biophys Res Commun
; 657: 16-23, 2023 05 21.
Article
in English
| MEDLINE | ID: covidwho-2288999
ABSTRACT
PF-07321332 and PF-07304814, inhibitors against SARS-CoV-2 developed by Pfizer, exhibit broad-spectrum inhibitory activity against the main protease (Mpro) from various coronaviruses. Structures of PF-07321332 or PF-07304814 in complex with Mpros of various coronaviruses reveal their inhibitory mechanisms against different Mpros. However, the structural information on the lower pathogenic coronavirus Mpro with PF-07321332 or PF-07304814 is currently scarce, which hinders our comprehensive understanding of the inhibitory mechanisms of these two inhibitors. Meanwhile, given that some immunocompromised individuals are still affected by low pathogenic coronaviruses, we determined the structures of lower pathogenic coronavirus HCoV-229E Mpro with PF-07321332 and PF-07304814, respectively, and analyzed and defined in detail the structural basis for the inhibition of HCoV-229E Mpro by both inhibitors. Further, we compared the crystal structures of multiple coronavirus Mpro complexes with PF-07321332 or PF-07304814 to illustrate the differences in the interaction of Mpros, and found that the inhibition mechanism of lower pathogenic coronavirus Mpro was more similar to that of moderately pathogenic coronaviruses. Our structural studies provide new insights into drug development for low pathogenic coronavirus Mpro, and provide theoretical basis for further optimization of both inhibitors to contain potential future coronaviruses.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Coronavirus 229E, Human
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Biochem Biophys Res Commun
Year:
2023
Document Type:
Article
Affiliation country:
J.bbrc.2023.03.043
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