The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2

Abstract Bat coronavirus (CoV) RaTG13 shares the highest genome sequence identity with SARS-CoV-2 among all known coronaviruses, and also uses human angiotensin converting enzyme 2 (hACE2) for virus entry. Thus, SARS-CoV-2 is thought to have originated from bat. However, whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive. Here, we found that Rhinolophus affinis bat ACE2 (RaACE2) is an entry receptor for both SARS-CoV-2 and RaTG13, although RaACE2 binding to the receptor binding domain (RBD) of SARS-CoV-2 is markedly weaker than that of hACE2. We further evaluated the receptor activities of ACE2s from additional 16 diverse animal species for RaTG13, SARS-CoV, and SARS-CoV-2 in terms of S protein binding, membrane fusion, and pseudovirus entry. We found that the RaTG13 spike (S) protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2, and seven out of sixteen different ACE2s function as entry receptors for all three viruses, indicating that all three viruses might have broad host rages. Of note, RaTG13 S pseudovirions can use mouse, but not pangolin ACE2, for virus entry, whereas SARS-CoV-2 S pseudovirions can use pangolin, but limited for mouse, ACE2s enter cells. Mutagenesis analysis revealed that residues 484 and 498 in RaTG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2. Finally, two polymorphous Rhinolophous sinicus bat ACE2s showed different susceptibilities to virus entry by RaTG13 and SARS-CoV-2 S pseudovirions, suggesting possible coevolution. Our results offer better understanding of the mechanism of coronavirus entry, host range, and virus-host coevolution..

Medienart:

Preprint

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021

Sprache:

Englisch

Beteiligte Personen:

Li, Pei [VerfasserIn]
Guo, Ruixuan [VerfasserIn]
Liu, Yan [VerfasserIn]
Zhang, Yintgtao [VerfasserIn]
Hu, Jiaxin [VerfasserIn]
Ou, Xiuyuan [VerfasserIn]
Mi, Dan [VerfasserIn]
Chen, Ting [VerfasserIn]
Mu, Zhixia [VerfasserIn]
Han, Yelin [VerfasserIn]
Cui, Zhewei [VerfasserIn]
Zhang, Leiliang [VerfasserIn]
Wang, Xinquan [VerfasserIn]
Wu, Zhiqiang [VerfasserIn]
Wang, Jianwei [VerfasserIn]
Jin, Qi [VerfasserIn]
Qian, Zhaohui [VerfasserIn]

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doi:

10.1101/2020.11.16.385849

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI019360495