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Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption.
Ren, Wenlin; Lan, Jun; Ju, Xiaohui; Gong, Mingli; Long, Quanxin; Zhu, Zihui; Yu, Yanying; Wu, Jianping; Zhong, Jin; Zhang, Rong; Fan, Shilong; Zhong, Guocai; Huang, Ailong; Wang, Xinquan; Ding, Qiang.
  • Ren W; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
  • Lan J; Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
  • Ju X; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
  • Gong M; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
  • Long Q; Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
  • Zhu Z; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
  • Yu Y; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
  • Wu J; Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China.
  • Zhong J; Unit of Viral Hepatitis, Institut Pasteur of Shanghai, CAS Key Laboratory of Molecular Virology and Immunology, Chinese Academy of Sciences, Shanghai, China.
  • Zhang R; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Fudan University, Shanghai, China.
  • Fan S; Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
  • Zhong G; Shenzhen Bay Laboratory, Shenzhen, China.
  • Huang A; School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
  • Wang X; Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
  • Ding Q; Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
PLoS Pathog ; 17(11): e1010053, 2021 11.
Article in English | MEDLINE | ID: covidwho-1506691
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ABSTRACT
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / Host Adaptation / SARS-CoV-2 / COVID-19 / Mink / Mutation Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged / Young adult Country/Region as subject: Europa Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1010053

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / Host Adaptation / SARS-CoV-2 / COVID-19 / Mink / Mutation Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged / Young adult Country/Region as subject: Europa Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1010053