9VUT

Crystal structure of SADS-CoV main protease (Lys35Val)

9VUT の概要

• エントリーDOI: 10.2210/pdb9vut/pdb
• 分子名称: ORF1ab polyprotein (2 entities in total)
• 機能のキーワード: swine acute diarrhea syndrome coronavirus, main protease, viral protein
• 由来する生物種: Swine acute diarrhea syndrome coronavirus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65023.62

構造登録者

Zeng, R.,Lei, J. (登録日: 2025-07-14, 公開日: 2026-02-18, 最終更新日: 2026-03-18)

主引用文献

Zeng, R.,Cui, S.,Xia, X.,Huang, C.,Sun, J.,Deng, X.,Gui, Q.,Fan, H.,Liu, X.,Yu, Y.,Yang, S.,Lei, J.
An intrinsic loop-mediated structural stability modulating inhibitor potency in the SADS-CoV and SARS-CoV-2 main proteases.
Plos Pathog., 22:e1013981-e1013981, 2026

PubMed Abstract: Swine acute diarrhea syndrome coronavirus (SADS-CoV) poses a significant zoonotic risk. The absence of the structure of SADS-CoV main protease (Mpro) severely impedes the development of effective antiviral therapeutics. Here, we present the high-resolution structures of SADS-CoV Mpro and its complexes with inhibitors 27h and SY110, respectively. These two compounds inhibit SADS-CoV Mpro through a novel inhibition mechanism. Residues 40-53 of SADS-CoV Mpro adopt a single-helix conformation, in contrast to a coiled coil formed by two consecutive alpha-helices observed in SARS-CoV-2 Mpro. These structural differences contribute to the varying inhibitor potency between Alphacoronavirus (α-CoV) and Betacoronavirus (β-CoV) Mpros. We subsequently demonstrate that the absence of residue '51' in α-CoV Mpros plays a key role in these conformational changes. Furthermore, 27h was proved to efficiently suppress SADS-CoV replication in both cell-based assays and porcine intestinal organoids-marking the first such assessment. Overall, these findings reveal that intrinsic Mpro dynamics influence inhibitor potency and provide insights for designing broad-spectrum Mpro inhibitors.

PubMed: 41734227
DOI: 10.1371/journal.ppat.1013981

実験手法

X-RAY DIFFRACTION (2.14 Å)