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Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway.
Jie Zhou; Thomas P Peacock; Jonathan C Brown; Daniel H. Goldhill; Ahmed M.E. Elrefaey; Rebekah Penrice-Randal; Vanessa M. Cowton; Giuditta De Lorenzo; Wilhelm Furnon; William T. Harvey; Ruthiran Kugathasan; Rebecca Frise; Laury Baillon; Ria Lassauniere; Nazia Thakur; Giulia Gallo; Hannah Goldswain; Xiaofeng Dong; Nadine P. Randle; Fiachra Sweeney; Martha C. Glynn; Jessica L. Quantrill; Paul F. McKay; Arvind H. Patel; Massimo Palmarini; Julian A. Hiscox; Dalan Bailey; Wendy S. Barclay.
Afiliación
  • Jie Zhou; Department of Infectious Diseases, Imperial College London, UK, W2 1PG
  • Thomas P Peacock; Department of Infectious Diseases, Imperial College London, UK, W2 1PG
  • Jonathan C Brown; Department of Infectious Diseases, Imperial College London, UK, W2 1PG
  • Daniel H. Goldhill; Department of Infectious Diseases, Imperial College London, UK, W2 1PG
  • Ahmed M.E. Elrefaey; The Pirbright Institute, Woking, Surrey, UK, GU24 0NF
  • Rebekah Penrice-Randal; Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, UK, L3 5RF
  • Vanessa M. Cowton; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • Giuditta De Lorenzo; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • Wilhelm Furnon; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • William T. Harvey; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • Ruthiran Kugathasan; Department of Infectious Diseases, Imperial College London, UK, W2 1PG
  • Rebecca Frise; Department of Infectious Diseases, Imperial College London, UK, W2 1PG
  • Laury Baillon; Department of Infectious Diseases, Imperial College London, UK, W2 1PG
  • Ria Lassauniere; Virus & Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark.
  • Nazia Thakur; The Pirbright Institute, Woking, Surrey, UK, GU24 0NF
  • Giulia Gallo; The Pirbright Institute, Woking, Surrey, UK, GU24 0NF
  • Hannah Goldswain; Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, UK, L3 5RF
  • Xiaofeng Dong; Institute for Infection, Veterinary and Ecological Sciences, University of Liverpool, UK.
  • Nadine P. Randle; Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, UK, L3 5RF
  • Fiachra Sweeney; Department of Infectious Disease, Imperial College London, UK, W2 1PG
  • Martha C. Glynn; Department of Infectious Disease, Imperial College London, UK, W2 1PG
  • Jessica L. Quantrill; Department of Infectious Disease, Imperial College London, UK, W2 1PG
  • Paul F. McKay; Department of Infectious Disease, Imperial College London, UK, W2 1PG
  • Arvind H. Patel; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • Massimo Palmarini; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • Julian A. Hiscox; Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, UK, L3 5RF
  • Dalan Bailey; The Pirbright Institute, Woking, Surrey, UK, GU24 0NF
  • Wendy S. Barclay; Department of Infectious Diseases, Imperial College London, UK, W2 1PG
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-456972
ABSTRACT
SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs and farmed mink. Since the start of the 2019 pandemic several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all 3 mink-adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.
Licencia
cc_by_nc
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Observational_studies / Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Observational_studies / Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint