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


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.

SUBMITTER: Tang L 

PROVIDER: S-EPMC9305271 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Tang Lingfeng L   Zhang Di D   Han Pu P   Kang Xinrui X   Zheng Anqi A   Xu Zepeng Z   Zhao Xin X   Wang Vivien Ya-Fan VY   Qi Jianxun J   Wang Qihui Q   Liu Kefang K   Gao George F GF  

International journal of biological sciences 20220711 12


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 b  ...[more]

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