Download MendeleyStructural basis for the inhibition of coronaviral main proteases by PF-00835231.
Zhou, X., Lu, X., Lin, C., Zou, X., Li, W., Zeng, X., Wang, J., Zeng, P., Wang, W., Zhang, J., Jiang, H., Li, J.(2024) Acta Biochim Biophys Sin (Shanghai) 56: 1813-1822
- PubMed: 39076076
- DOI: https://doi.org/10.3724/abbs.2024122
- Primary Citation of Related Structures:
8J32, 8J34, 8J35, 8J36, 8J37, 8J38, 8J39, 8J3A, 8J3B - PubMed Abstract:
The main protease (M pro ) of coronaviruses plays a key role in viral replication, thus serving as a hot target for drug design. PF-00835231 is a promising inhibitor of SARS-CoV-2 M pro . Here, we report the inhibitory potency of PF-00835231 against SARS-CoV-2 M pro and seven M pro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) from SARS-CoV-2 variants. The results confirm that PF-00835231 has broad-spectrum inhibition against various coronaviral M pro s. In addition, the crystal structures of SARS-CoV-2 M pro , SARS-CoV M pro , MERS-CoV M pro , and seven SARS-CoV-2 M pro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) in complex with PF-00835231 are solved. A detailed analysis of these structures reveals key determinants essential for inhibition and elucidates the binding modes of different coronaviral M pro s. Given the importance of the main protease for the treatment of coronaviral infection, structural insights into M pro inhibition by PF-00835231 can accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.
Organizational Affiliation:
College of Pharmacy, Gannan Medical University, Ganzhou 341000, China.
