Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption

COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as “Cluster 5” that contained mutations in the spike...

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Autores principales:	Wenlin Ren, Jun Lan, Xiaohui Ju, Mingli Gong, Quanxin Long, Zihui Zhu, Yanying Yu, Jianping Wu, Jin Zhong, Rong Zhang, Shilong Fan, Guocai Zhong, Ailong Huang, Xinquan Wang, Qiang Ding
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0b6cdd28244544f28abb3124f2f2b2d1
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spelling	oai:doaj.org-article:0b6cdd28244544f28abb3124f2f2b2d12021-11-25T05:46:51ZMutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption1553-73661553-7374https://doaj.org/article/0b6cdd28244544f28abb3124f2f2b2d12021-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601601/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as “Cluster 5” that contained mutations in the spike protein. However, the functional properties of these “Cluster 5” mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks. Author summary Employees infected with SARS-CoV-2 transmitted the virus to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant “Cluster 5” with four amino acid changes in the spike protein. We demonstrated that the one of the mutations-Y453F as an adaptive mutation increased virus interaction with mink ACE2 receptor, without compromising its utilization of human ACE2 receptor. In addition, miSARS-CoV-2 exhibited resistance to convalescent sera from COVID-19 patients and still sensitive to ACE2-based therapeutic strategy. Therefore, it is urgently needed to identify the potential zoonotic reservoirs, and monitor the evolution of virus in the zoonotic host to prevent future outbreaks and develop countermeasures accordingly.Wenlin RenJun LanXiaohui JuMingli GongQuanxin LongZihui ZhuYanying YuJianping WuJin ZhongRong ZhangShilong FanGuocai ZhongAilong HuangXinquan WangQiang DingPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Wenlin Ren Jun Lan Xiaohui Ju Mingli Gong Quanxin Long Zihui Zhu Yanying Yu Jianping Wu Jin Zhong Rong Zhang Shilong Fan Guocai Zhong Ailong Huang Xinquan Wang Qiang Ding Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption
description	COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as “Cluster 5” that contained mutations in the spike protein. However, the functional properties of these “Cluster 5” mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks. Author summary Employees infected with SARS-CoV-2 transmitted the virus to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant “Cluster 5” with four amino acid changes in the spike protein. We demonstrated that the one of the mutations-Y453F as an adaptive mutation increased virus interaction with mink ACE2 receptor, without compromising its utilization of human ACE2 receptor. In addition, miSARS-CoV-2 exhibited resistance to convalescent sera from COVID-19 patients and still sensitive to ACE2-based therapeutic strategy. Therefore, it is urgently needed to identify the potential zoonotic reservoirs, and monitor the evolution of virus in the zoonotic host to prevent future outbreaks and develop countermeasures accordingly.
format	article
author	Wenlin Ren Jun Lan Xiaohui Ju Mingli Gong Quanxin Long Zihui Zhu Yanying Yu Jianping Wu Jin Zhong Rong Zhang Shilong Fan Guocai Zhong Ailong Huang Xinquan Wang Qiang Ding
author_facet	Wenlin Ren Jun Lan Xiaohui Ju Mingli Gong Quanxin Long Zihui Zhu Yanying Yu Jianping Wu Jin Zhong Rong Zhang Shilong Fan Guocai Zhong Ailong Huang Xinquan Wang Qiang Ding
author_sort	Wenlin Ren
title	Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption
title_short	Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption
title_full	Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption
title_fullStr	Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption
title_full_unstemmed	Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption
title_sort	mutation y453f in the spike protein of sars-cov-2 enhances interaction with the mink ace2 receptor for host adaption
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/0b6cdd28244544f28abb3124f2f2b2d1
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Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption

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