8WZP

Crystal structure of SARS-Cov-2 main protease M49I mutant in complex with CCF0058981

8WZP の概要

• エントリーDOI: 10.2210/pdb8wzp/pdb
• 分子名称: 3C-like proteinase nsp5, 2-(benzotriazol-1-yl)-~{N}-[(3-chlorophenyl)methyl]-~{N}-[4-(1~{H}-imidazol-5-yl)phenyl]ethanamide (3 entities in total)
• 機能のキーワード: viral protein-inhibitor complex, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67062.92

構造登録者

Jiang, H.H.,Zou, X.F.,Zhou, X.L.,Zhang, J.,Li, J. (登録日: 2023-11-02, 公開日: 2024-04-17)

主引用文献

Jiang, H.,Zou, X.,Zhou, X.,Zhang, J.,Li, J.
Crystal structure of SARS-CoV-2 main protease (M pro ) mutants in complex with the non-covalent inhibitor CCF0058981.
Biochem.Biophys.Res.Commun., 692:149352-149352, 2024

PubMed Abstract: SARS-CoV-2 constantly circulates and evolves worldwide, generating many variants and posing a menace to global health. It is urgently needed to discover effective medicines to treat the disease caused by SARS-CoV-2 and its variants. An established target for anti-SARS-CoV-2 drug discovery is the main protease (M), since it exerts an irreplaceable action in viral life cycle. CCF0058981, derived from ML300, is a non-covalent inhibitor that exhibits low nanomolar potency against SARS-CoV-2 M and submicromolar anti-SARS-CoV-2 activity, thereby providing a valuable starting point for drug design. However, structural basis underlying inhibition of SARS-CoV-2 M by CCF0058981 remains undetermined. In this study, the crystal structures of CCF0058981 in complex with two SARS-CoV-2 M mutants (M49I and V186F), which have been identified in the recently emerged Omicron subvariants, were solved. Structural analysis defined the pivotal molecular factors responsible for the interactions between CCF0058981 and these two M mutants, and revealed the binding modes of CCF0058981 to M M49I and V186F mutants. These data not only provide structural insights for SARS-CoV-2 M inhibition by CCF0058981, but also add to develop effective broad-spectrum drugs against SARS-CoV-2 as well as its variants.

PubMed: 38056159
DOI: 10.1016/j.bbrc.2023.149352

実験手法

X-RAY DIFFRACTION (1.76 Å)