9JJ6

BtHKU5-CoV-2-441 Spike RBD domain binding to hACE2

Summary for 9JJ6

• Entry DOI: 10.2210/pdb9jj6/pdb
• EMDB information: 61517
• Descriptor: BtHKU5-CoV-2-441 Spike RBD domain, Processed angiotensin-converting enzyme 2, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: rbd-receptor complex, virus entry, zoonotic, viral protein/hydrolase, viral protein-hydrolase complex
• Biological source: Pipistrellus bat coronavirus HKU5; More
• Total number of polymer chains: 2
• Total formula weight: 98168.18

Authors

Zhang, W.,Peng, W.,Chen, H.Y. (deposition date: 2024-09-13, release date: 2025-03-12, Last modification date: 2025-04-02)

Primary citation

Chen, J.,Zhang, W.,Li, Y.,Liu, C.,Dong, T.,Chen, H.,Wu, C.,Su, J.,Li, B.,Zhang, W.,Hu, B.,Jia, J.,Ma, C.B.,Zhu, Y.,He, X.,Li, A.,Pan, K.,Lin, H.,Guo, Z.,Li, C.,Zhang, L.,Yan, H.,Zhou, P.,Peng, W.,Shi, Z.L.
Bat-infecting merbecovirus HKU5-CoV lineage 2 can use human ACE2 as a cell entry receptor.
Cell, 188:1729-1742.e16, 2025

PubMed Abstract: Merbecoviruses comprise four viral species with remarkable genetic diversity: MERS-related coronavirus, Tylonycterisbat coronavirus HKU4, Pipistrellusbat coronavirus HKU5, and Hedgehog coronavirus 1. However, the potential human spillover risk of animal merbecoviruses remains to be investigated. Here, we reported the discovery of HKU5-CoV lineage 2 (HKU5-CoV-2) in bats that efficiently utilize human angiotensin-converting enzyme 2 (ACE2) as a functional receptor and exhibits a broad host tropism. Cryo-EM analysis of HKU5-CoV-2 receptor-binding domain (RBD) and human ACE2 complex revealed an entirely distinct binding mode compared with other ACE2-utilizing merbecoviruses with RBD footprint largely shared with ACE2-using sarbecoviruses and NL63. Structural and functional analyses indicate that HKU5-CoV-2 has a better adaptation to human ACE2 than lineage 1 HKU5-CoV. Authentic HKU5-CoV-2 infected human ACE2-expressing cell lines and human respiratory and enteric organoids. This study reveals a distinct lineage of HKU5-CoVs in bats that efficiently use human ACE2 and underscores their potential zoonotic risk.

PubMed: 39970913
DOI: 10.1016/j.cell.2025.01.042

Experimental method

ELECTRON MICROSCOPY (2.94 Å)