Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway.

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Zhou, Jie, Peacock, Thomas, Brown, Jonathan ORCID: 0000-0001-6849-3962, Goldhill, Daniel, Elrefaey, Ahmed, Penrice-Randal, Rebekah ORCID: 0000-0002-0653-2097, Cowton, Vanessa, De Lorenzo, Giuditta, Furnon, Wilhelm, Harvey, William et al (show 19 more authors) , Kugathasan, Ruthiran, Frise, Rebecca, Baillon, Laury, Lassauniere, Ria, Thakur, Nazia, Gallo, Giulia, Goldswain, Hannah ORCID: 0000-0003-4194-8714, Donovan-Banfield, I'ah ORCID: 0000-0002-5124-2427, Dong, Xiaofeng, Randle, Nadine ORCID: 0000-0002-3775-9585, Sweeney, Fiachra, Glynn, Martha, Quantrill, Jessica, McKay, Paul, Patel, Arvind, Palmarini, Massimo, Hiscox, Julian ORCID: 0000-0002-6582-0275, Bailey, Dalan and Barclay, Wendy ORCID: 0000-0002-3948-0895 (2021) Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway. Cell Rep, 38 (6). 110344-.

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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.

Item Type:	Article
Uncontrolled Keywords:	ACE2, COVID-19, SARS-CoV-2, antigenicity, coronavirus, ferret, mink, pandemic, zoonosis, Adaptation, Biological, Animals, COVID-19, Ferrets, Genetic Fitness, Humans, Mink, Mutation, Pandemics, Respiratory System, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Viral Zoonoses
Divisions:	Faculty of Health and Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	18 May 2022 14:05
Last Modified:	15 Mar 2024 06:44
DOI:	10.21203/rs.3.rs-829214/v1
Open Access URL:	https://www.sciencedirect.com/science/article/pii/...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3155039