Tags

Type your tag names separated by a space and hit enter

Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants.
J Virol. 2022 09 14; 96(17):e0081422.JV

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), have been identified in mink-derived viruses. Here, we examined binding of the mink angiotensin-converting enzyme 2 (ACE2) receptor to mink-derived and important human-originating variants, and we demonstrated that most of the RBD variants increased the binding affinities to mink ACE2 (mkACE2). Cryo-electron microscopy structures of the mkACE2-RBD Y453F (with a Y-to-F change at position 453) and mkACE2-RBD F486L complexes helped identify the key residues that facilitate changes in mkACE2 binding affinity. Additionally, the data indicated that the Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and human vaccinated sera efficiently prevented infection of human cells by pseudoviruses expressing Y453F, F486L, or N501T RBD. Our findings provide an important molecular mechanism for the rapid adaptation of SARS-CoV-2 in minks and highlight the potential influence of the main mink-originating variants for humans. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a broad range of hosts. Mink-derived SARS-CoV-2 can transmit back to humans. There is an urgent need to understand the binding mechanism of mink-derived SARS-CoV-2 variants to mink receptor. In this study, we identified all mutations in the receptor-binding domain (RBD) of spike (S) protein from mink-derived SARS-CoV-2, and we demonstrated the enhanced binding affinity of mink angiotensin-converting enzyme 2 (ACE2) to most of the mink-derived RBD variants as well as important human-originating RBD variants. Cryo-electron microscopy structures revealed that the Y453F and F486L mutations enhanced the binding forces in the interaction interface. In addition, Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and the SARS-CoV-2 pseudoviruses with Y453F, F486L, or N501T mutations were neutralized by human vaccinated sera. Therefore, our results provide valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2.

Authors+Show Affiliations

Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. College of Life Sciences, Jiangxi Science and Technology Normal University, Nanchang, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. College of Life Science and Technology, Southeast University, Nanjing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. University of the Chinese Academy of Sciences, Beijing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. College of Veterinary Medicine, China Agricultural University, Beijing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. School of Life Sciences, Shanxi University, Taiyuan, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. College of Life Science and Technology, Southeast University, Nanjing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. Institutes of Physical Science and Information Technology, Anhui University, Hefei, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. CAS Center for Influenza Research and Early-Warning, Chinese Academy of Sciences, Beijing, China.Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. College of Life Sciences, Jiangxi Science and Technology Normal University, Nanchang, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36000849

Citation

Su, Chao, et al. "Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants." Journal of Virology, vol. 96, no. 17, 2022, pp. e0081422.
Su C, He J, Han P, et al. Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants. J Virol. 2022;96(17):e0081422.
Su, C., He, J., Han, P., Bai, B., Li, D., Cao, J., Tian, M., Hu, Y., Zheng, A., Niu, S., Chen, Q., Rong, X., Zhang, Y., Li, W., Qi, J., Zhao, X., Yang, M., Wang, Q., & Gao, G. F. (2022). Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants. Journal of Virology, 96(17), e0081422. https://doi.org/10.1128/jvi.00814-22
Su C, et al. Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants. J Virol. 2022 09 14;96(17):e0081422. PubMed PMID: 36000849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants. AU - Su,Chao, AU - He,Juanhua, AU - Han,Pengcheng, AU - Bai,Bin, AU - Li,Dedong, AU - Cao,Jian, AU - Tian,Mingxiong, AU - Hu,Yu, AU - Zheng,Anqi, AU - Niu,Sheng, AU - Chen,Qian, AU - Rong,Xiaoyu, AU - Zhang,Yanfang, AU - Li,Weiwei, AU - Qi,Jianxun, AU - Zhao,Xin, AU - Yang,Mengsu, AU - Wang,Qihui, AU - Gao,George Fu, Y1 - 2022/08/24/ PY - 2022/8/25/pubmed PY - 2022/9/17/medline PY - 2022/8/24/entrez KW - ACE2 KW - F486L KW - N501T KW - SARS-CoV-2 KW - Y453F KW - cryo-EM structure KW - mink KW - virus entry SP - e0081422 EP - e0081422 JF - Journal of virology JO - J Virol VL - 96 IS - 17 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), have been identified in mink-derived viruses. Here, we examined binding of the mink angiotensin-converting enzyme 2 (ACE2) receptor to mink-derived and important human-originating variants, and we demonstrated that most of the RBD variants increased the binding affinities to mink ACE2 (mkACE2). Cryo-electron microscopy structures of the mkACE2-RBD Y453F (with a Y-to-F change at position 453) and mkACE2-RBD F486L complexes helped identify the key residues that facilitate changes in mkACE2 binding affinity. Additionally, the data indicated that the Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and human vaccinated sera efficiently prevented infection of human cells by pseudoviruses expressing Y453F, F486L, or N501T RBD. Our findings provide an important molecular mechanism for the rapid adaptation of SARS-CoV-2 in minks and highlight the potential influence of the main mink-originating variants for humans. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a broad range of hosts. Mink-derived SARS-CoV-2 can transmit back to humans. There is an urgent need to understand the binding mechanism of mink-derived SARS-CoV-2 variants to mink receptor. In this study, we identified all mutations in the receptor-binding domain (RBD) of spike (S) protein from mink-derived SARS-CoV-2, and we demonstrated the enhanced binding affinity of mink angiotensin-converting enzyme 2 (ACE2) to most of the mink-derived RBD variants as well as important human-originating RBD variants. Cryo-electron microscopy structures revealed that the Y453F and F486L mutations enhanced the binding forces in the interaction interface. In addition, Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and the SARS-CoV-2 pseudoviruses with Y453F, F486L, or N501T mutations were neutralized by human vaccinated sera. Therefore, our results provide valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/36000849/Molecular_Basis_of_Mink_ACE2_Binding_to_SARS_CoV_2_and_Its_Mink_Derived_Variants_ L2 - https://journals.asm.org/doi/abs/10.1128/jvi.00814-22?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -