9JCY

Crystal structure of the HCoV-HKU1 RBD in complex with Fab

9JCY の概要

• エントリーDOI: 10.2210/pdb9jcy/pdb
• 分子名称: Spike protein S1, Heavy chain of Fab, Light chain of Fab, ... (6 entities in total)
• 機能のキーワード: complex, antibody, hcov-hku1, antiviral protein
• 由来する生物種: Human coronavirus HKU1 (isolate N1); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 83328.25

構造登録者

Wang, H.,Zhao, Z.,Liu, X.,Duan, Y.,Yang, H. (登録日: 2024-08-30, 公開日: 2025-07-30)

主引用文献

Zhao, Z.,Yang, Q.,Liu, X.,Li, M.,Duan, Y.,Du, M.,Zhou, A.,Liu, H.,He, Y.,Wang, W.,Lu, Y.,Zhang, X.,Wang, H.,Yang, X.,Zhang, H.,Chen, X.,Rao, Z.,Yang, H.
The crystal structure of coronavirus RBD-TMPRSS2 complex provides basis for the discovery of therapeutic antibodies.
Nat Commun, 16:6636-6636, 2025

PubMed Abstract: HCoV-HKU1, one of seven human coronaviruses (HCoVs) that have harmful effects on human health, accounts for a substantial portion of common cold cases and can cause severe respiratory diseases in certain populations. Currently, effective antiviral treatments against this virus are limited. Recently, TMPRSS2, a host protease long acknowledged for its role in priming the spike proteins of various CoVs and promoting viral entry, was identified as a functional receptor for HCoV-HKU1, opening an avenue for anti-HCoV-HKU1 therapy development. In this study, we elucidate the detailed molecular mechanism underlying the interaction between the HCoV-HKU1 receptor-binding domain (RBD) and TMPRSS2 via crystallography. Guided by these structural insights, we successfully develop two types of therapeutic antibodies against HCoV-HKU1. The first type neutralizes the RBD, potently disrupting its interaction with TMPRSS2 and preventing viral infection. The second type targets TMPRSS2, inhibiting its enzymatic activity and/or interfering with its binding to the RBD. The latter demonstrates broad-spectrum anti-CoV activity, as the enzymatic activity of TMPRSS2 is crucial for both HCoV-HKU1 infection and other CoV infections. Our findings provide crucial structural insights into the recognition of TMPRSS2 by HCoV-HKU1 and offer promising antibody-based strategies for combating HCoV-HKU1 and other CoV infections.

PubMed: 40681508
DOI: 10.1038/s41467-025-62023-2

実験手法

X-RAY DIFFRACTION (1.8 Å)