7PKI

Crystal structure of human ACE2 bound to the spike receptor-binding domain from a cave bat sarbecovirus closely related to SARS-CoV-2.

7PKI の概要

• エントリーDOI: 10.2210/pdb7pki/pdb
• 分子名称: Processed angiotensin-converting enzyme 2, GLYCEROL, BANAL 236 coronavirus spike receptor-binding domain, ... (11 entities in total)
• 機能のキーワード: coronavirus, receptor binding domain, human ace2., viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94118.40

構造登録者

Baquero, E.,Rey, F.A. (登録日: 2021-08-25, 公開日: 2022-01-19, 最終更新日: 2024-10-09)

主引用文献

Temmam, S.,Vongphayloth, K.,Baquero, E.,Munier, S.,Bonomi, M.,Regnault, B.,Douangboubpha, B.,Karami, Y.,Chretien, D.,Sanamxay, D.,Xayaphet, V.,Paphaphanh, P.,Lacoste, V.,Somlor, S.,Lakeomany, K.,Phommavanh, N.,Perot, P.,Dehan, O.,Amara, F.,Donati, F.,Bigot, T.,Nilges, M.,Rey, F.A.,van der Werf, S.,Brey, P.T.,Eloit, M.
Bat coronaviruses related to SARS-CoV-2 and infectious for human cells.
Nature, 604:330-336, 2022

PubMed Abstract: The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats, including the closest virus from R. affinis, RaTG13 (refs. ), and pangolins. SARS-CoV-2 has a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 (hACE2) pathway have not yet been identified, although they would be key in understanding the origin of the epidemic. Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula. We found that the receptor-binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than that of the SARS-CoV-2 strain isolated in Wuhan from early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies that neutralize SARS-CoV-2. None of these bat viruses contains a furin cleavage site in the spike protein. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses that are potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.

PubMed: 35172323
DOI: 10.1038/s41586-022-04532-4

実験手法

X-RAY DIFFRACTION (2.94234133444 Å)