9lug | pdb_00009lug

Crystal structure of SARS-Cov-2 main protease E166V mutant in complex with Bofutrelvir

spinqualitylabelsall models 9lug, resolution 2.13Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9lug is a 2 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.13Å Ligands: FHR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A7U3EXT3_SARS2 Publication Abstract from PubMed The COVID-19 pandemic has caused significant global health and economic disruption. Mutations E166N, E166R, E166N, S144A and His163A in the SARS-CoV-2 main protease (M(pro)) have been implicated in reducing the efficacy of certain antiviral treatments. Bofutrelvir, a promising inhibitor, has shown effectiveness against SARS-CoV-2 M(pro). This study aims to evaluate the inhibitory effects of Bofutrelvir on the E166N, E166R, His163A, E166V and S144A mutants of SARS-CoV-2 M(pro), as well as on MERS-CoV M(pro). Our findings indicate a substantial reduction in the inhibitory potency of Bofutrelvir against these mutants and MERS-CoV, with IC(50) values significantly higher than those for the wild-type SARS-CoV-2 M(pro). Specifically, the E166N, E166R, E166V, S144A, and H163A mutations significantly reduce the binding affinity and inhibitory effectiveness of Bofutrelvir due to disrupted hydrogen bonds, altered binding site stability, and reduced enzyme activity. Structural analysis of the crystal complexes showed that changes in interactions at the S1 subsite in the mutants and the loss of hydrogen bonds at the S4 subsite in MERS-CoV M(pro) are critical factors contributing to the diminished inhibitory activity. These insights reveal the necessity of ongoing structural analysis to adapt therapeutic strategies. Inhibitory efficacy and structural insights of Bofutrelvir against SARS-CoV-2 M(pro) mutants and MERS-CoV M(pro).,Wang W, Zhou X, Li W, Zeng P, Guo L, Wang Q, Li J Commun Biol. 2025 Mar 25;8(1):493. doi: 10.1038/s42003-025-07929-9. PMID:40133408 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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