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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.
PMID 35874946 2022 Int J Biol Sci eng epublish
PubMed DOI Browse context

Article

Publication summary

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic. Intermediate horseshoe bats (<i>Rhinolophus affinis</i>) 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.

bACE2-Ra intermediate horseshoe bats SARS-CoV-2 SARS-CoV-2 variants structure Angiotensin-Converting Enzyme 2 Chiroptera SARS-CoV-2 Animals Protein Binding SARS-CoV-2 variants

Structured evidence records

Evidence records

2 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

An E35K substitution in horseshoe bat ACE2 increases binding affinity to the SARS-CoV-2 RBD through electrostatic interaction with residue E484, indicating molecular adaptation affecting receptor binding and cross-species compatibility.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

The E35K substitution, existing in other species, significantly enhanced the binding affinity owing to its electrostatic attraction with E484 of SARS-CoV-2 RBD.

Genes or proteins
RBD; ACE2
Receptors
ACE2
Mutations
E35K; E484
Mechanism types
receptor_binding; cell_entry
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

SARS-CoV-2 receptor-binding domain forms a crystal complex with intermediate horseshoe bat ACE2, demonstrating structural receptor compatibility and supporting viral entry.

Virus
SARS-CoV-2
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. A 3.3 Å resolution crystal structure of the bACE2-Ra/SARS-CoV-2 RBD complex was determined.

Method
binding assay; crystal structure determination; pseudovirus infection assay
Receptors
ACE2