OmniVira

Structural basis of SARS-CoV-2 and its variants binding to intermediate horseshoe bat ACE2.

Lingfeng Tang1,2 Di Zhang1,2 Pu Han1 Xinrui Kang1,3 Anqi Zheng1,3 Zepeng Xu1,2 Xin Zhao1 Vivien Ya-Fan Wang2 Jianxun Qi1,3 Qihui Wang1,3 Kefang Liu1 George F Gao1,2
Affiliations 3 institutions
  1. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  2. Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
  3. University of Chinese Academy of Sciences, Beijing 100049, China.
PMID35874946 DOI10.7150/ijbs.73640 Year2022 Journal International journal of biological sciences Int J Biol Sci Languageeng Statusepublish

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic. Intermediate horseshoe bats (Rhinolophus affinis) are hosts of RaTG13, the second most phylogenetically related viruses to SARS-CoV-2. We report the binding between intermediate horseshoe bat ACE2 (bACE2-Ra) and SARS-CoV-2 receptor-binding domain (RBD), supporting the pseudotyped SARS-CoV-2 viral infection. A 3.3 Å resolution crystal structure of the bACE2-Ra/SARS-CoV-2 RBD complex was determined. The interaction networks of Patch 1 showed differences in R34 and E35 of bACE2-Ra compared to hACE2 and big-eared horseshoe bat ACE2 (bACE2-Rm). The E35K substitution, existing in other species, significantly enhanced the binding affinity owing to its electrostatic attraction with E484 of SARS-CoV-2 RBD. Furthermore, bACE2-Ra showed extensive support for the SARS-CoV-2 variants. These results broaden our knowledge of the ACE2/RBD interaction mechanism and emphasize the importance of continued surveillance of intermediate horseshoe bats to prevent spillover risk.

Supporting text Virus Host Location
bACE2-Ra 1 intermediate horseshoe bats 1 SARS-CoV-2 550 SARS-CoV-2 variants 88 structure 6 Angiotensin-Converting Enzyme 2 177 Chiroptera 371 SARS-CoV-2 453 Animals 1948 Protein Binding 193 SARS-CoV-2 variants 86

Evidence records

1 total
Experimental Infection
1 records · 1 evidence types
Evidence type Host Range Experiment
1 records
OVE6175 Host Range Experiment
Key finding

SARS-CoV-2 pseudotyped virus was able to infect cells expressing ACE2 from intermediate horseshoe bat (Rhinolophus affinis), demonstrating susceptibility of bat ACE2 to SARS-CoV-2 entry.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
intermediate horseshoe bat Rhinolophus affinis Experimental system
Location
Not specified
Supporting text

We report the binding between intermediate horseshoe bat ACE2 (bACE2-Ra) and SARS-CoV-2 receptor-binding domain (RBD), supporting the pseudotyped SARS-CoV-2 viral infection.

Method
pseudovirus infection assay | receptor-binding assay | crystal structure determination
Sample type
cells expressing intermediate horseshoe bat ACE2
Experimental system
pseudotyped virus infection system using cells expressing bat ACE2 receptor