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Molecular dynamic simulation analysis of SARS-CoV-2 spike mutations and evaluation of ACE2 from pets and wild animals for infection risk.
Comput Biol Chem. 2022 Feb; 96:107613.CB

Abstract

Coronavirus Disease 2019 (COVID-19) is an ongoing global health emergency that has caused tremendous stress and loss of life worldwide. The viral spike glycoprotein is a critical molecule mediating transmission of SARS-CoV-2 by interacting with human ACE2. However, through the course of the pandemics, there has not been a thorough analysis of the spike protein mutations, and on how these mutants influence the transmission of SARS-CoV-2. Besides, cases of SARS-CoV-2 infection among pets and wild animals have been reported, so the susceptibility of these animals requires great attention to investigate, as they may also link to the renewed question of a possible intermediate host for SARS-CoV-2 before it was transmitted to humans. With over 226,000 SARS-CoV-2 sequences obtained, we found 1573 missense mutations in the spike gene, and 226 of them were within the receptor-binding domain (RBD) region that directly interacts with human ACE2. Modeling the interactions between SARS-CoV-2 spike mutants and ACE2 molecules showed that most of the 74 missense mutations in the RBD region of the interaction interface had little impact on spike binding to ACE2, whereas several within the spike RBD increased the binding affinity toward human ACE2 thus making the virus likely more contagious. On the other hand, modeling the interactions between animal ACE2 molecules and SARS-CoV-2 spike revealed that many pets and wild animals' ACE2 had a variable binding ability. Particularly, ACE2 of bamboo rat had stronger binding to SARS-CoV-2 spike protein, whereas that of mole, vole, Mus pahari, palm civet, and pangolin had a weaker binding compared to human ACE2. Our results provide structural insights into the impact on interactions of the SARS-CoV-2 spike mutants to human ACE2, and shed light on SARS-CoV-2 transmission in pets and wild animals, and possible clues to the intermediate host(s) for SARS-CoV-2.

Authors+Show Affiliations

Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China; Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100039, China.West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences, Shanghai 200032, China.Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences, Shanghai 200032, China; University of Chinese Academy of Sciences, Beijing 100039, China. Electronic address: lixuan@sippe.ac.cn.West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China. Electronic address: lm_nutr@scu.edu.cn.Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China; Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100039, China. Electronic address: phao@ips.ac.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34896769

Citation

Chen, Ping, et al. "Molecular Dynamic Simulation Analysis of SARS-CoV-2 Spike Mutations and Evaluation of ACE2 From Pets and Wild Animals for Infection Risk." Computational Biology and Chemistry, vol. 96, 2022, p. 107613.
Chen P, Wang J, Xu X, et al. Molecular dynamic simulation analysis of SARS-CoV-2 spike mutations and evaluation of ACE2 from pets and wild animals for infection risk. Comput Biol Chem. 2022;96:107613.
Chen, P., Wang, J., Xu, X., Li, Y., Zhu, Y., Li, X., Li, M., & Hao, P. (2022). Molecular dynamic simulation analysis of SARS-CoV-2 spike mutations and evaluation of ACE2 from pets and wild animals for infection risk. Computational Biology and Chemistry, 96, 107613. https://doi.org/10.1016/j.compbiolchem.2021.107613
Chen P, et al. Molecular Dynamic Simulation Analysis of SARS-CoV-2 Spike Mutations and Evaluation of ACE2 From Pets and Wild Animals for Infection Risk. Comput Biol Chem. 2022;96:107613. PubMed PMID: 34896769.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular dynamic simulation analysis of SARS-CoV-2 spike mutations and evaluation of ACE2 from pets and wild animals for infection risk. AU - Chen,Ping, AU - Wang,Jingfang, AU - Xu,Xintian, AU - Li,Yuping, AU - Zhu,Yan, AU - Li,Xuan, AU - Li,Ming, AU - Hao,Pei, Y1 - 2021/12/01/ PY - 2021/11/17/received PY - 2021/11/29/accepted PY - 2021/12/14/pubmed PY - 2022/1/28/medline PY - 2021/12/13/entrez KW - ACE2 receptor recognition KW - Animal host KW - Molecular dynamics simulations KW - Molecular modeling KW - Mutations KW - SARS-CoV-2 spike protein SP - 107613 EP - 107613 JF - Computational biology and chemistry JO - Comput Biol Chem VL - 96 N2 - Coronavirus Disease 2019 (COVID-19) is an ongoing global health emergency that has caused tremendous stress and loss of life worldwide. The viral spike glycoprotein is a critical molecule mediating transmission of SARS-CoV-2 by interacting with human ACE2. However, through the course of the pandemics, there has not been a thorough analysis of the spike protein mutations, and on how these mutants influence the transmission of SARS-CoV-2. Besides, cases of SARS-CoV-2 infection among pets and wild animals have been reported, so the susceptibility of these animals requires great attention to investigate, as they may also link to the renewed question of a possible intermediate host for SARS-CoV-2 before it was transmitted to humans. With over 226,000 SARS-CoV-2 sequences obtained, we found 1573 missense mutations in the spike gene, and 226 of them were within the receptor-binding domain (RBD) region that directly interacts with human ACE2. Modeling the interactions between SARS-CoV-2 spike mutants and ACE2 molecules showed that most of the 74 missense mutations in the RBD region of the interaction interface had little impact on spike binding to ACE2, whereas several within the spike RBD increased the binding affinity toward human ACE2 thus making the virus likely more contagious. On the other hand, modeling the interactions between animal ACE2 molecules and SARS-CoV-2 spike revealed that many pets and wild animals' ACE2 had a variable binding ability. Particularly, ACE2 of bamboo rat had stronger binding to SARS-CoV-2 spike protein, whereas that of mole, vole, Mus pahari, palm civet, and pangolin had a weaker binding compared to human ACE2. Our results provide structural insights into the impact on interactions of the SARS-CoV-2 spike mutants to human ACE2, and shed light on SARS-CoV-2 transmission in pets and wild animals, and possible clues to the intermediate host(s) for SARS-CoV-2. SN - 1476-928X UR - https://www.unboundmedicine.com/medline/citation/34896769/Molecular_dynamic_simulation_analysis_of_SARS_CoV_2_spike_mutations_and_evaluation_of_ACE2_from_pets_and_wild_animals_for_infection_risk_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1476-9271(21)00183-3 DB - PRIME DP - Unbound Medicine ER -