Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway
Open accessAbstract
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 three 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.
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The F486L mutation has been shown to directly enhance entry into cells expressing mink or ferret ACE2.
“The F486L mutation has been shown to directly enhance entry into cells expressing mink or ferret ACE2 (ref. 12).”
From Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa (2022) · cites this paper as [12]
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Omicron breakthrough infections in vaccinated or previously infected hamsters
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Global landscape of the host response to SARS-CoV-2 variants reveals viral evolutionary trajectoriesPreprint
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Self-citationTransmissibility and pathogenicity of SARS-CoV-2 variants in animal models
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Risk assessment of SARS-CoV-2 replicating and evolving in animals
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Propylene glycol inactivates respiratory viruses and prevents airborne transmission
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Infectious droplet exposure is an inefficient route for SARS-CoV-2 infection in the ferret model
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Thinking Outside the Box: Utilizing Nontraditional Animal Models for COVID-19 Research
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Does having a cat in your house increase your risk of catching COVID-19?
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The panzootic potential of SARS-CoV-2
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Sequence signatures within the genome of SARS-CoV-2 can be used to predict host source
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Mycophenolic acid treatment drives the emergence of novel SARS-CoV-2 variants
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Self-citationWill animal reservoirs give us the next SARS-CoV-2 variant?
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Animal Ethics and Zoonosis Risks
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Using minor variant genomes and machine learning to study the genome biology of SARS-CoV-2 over time
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SARS-CoV-2 strains bearing Omicron BA.1 spike replicate in C57BL/6 mice
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Self-citationThe recurrent Spike A222V mutation in SARS-CoV-2 enhances replication in primary deer lung cells
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- Authors
- Zhou, J., Peacock, T. P., Brown, J. C., Goldhill, D. H., Elrefaey, A. M. E., Penrice-Randal, R., Cowton, V. M., De Lorenzo, G., Furnon, W., Harvey, W. T., Kugathasan, R., Frise, R., Baillon, L., Lassaunière, R., Thakur, N., Gallo, G., Goldswain, H., Donovan-Banfield, I., Dong, X., Randle, N. P., Sweeney, F., Glynn, M. C., Quantrill, J. L., McKay, P. F., Patel, A. H., Palmarini, M., Hiscox, J. A., Bailey, D., & Barclay, W. S.
- Affiliations
- Imperial College London (GB)
- The Pirbright Institute (GB)
- University of Liverpool (GB)
- MRC University of Glasgow Centre for Virus Research (GB)
- Statens Serum Institut (DK)
- Agency for Science, Technology and Research (SG)
- ORCID
- Zhou, Jie
- Peacock, Thomas P.
- Brown, Jonathan C.
- Goldhill, Daniel H.
- Elrefaey, Ahmed M.E.
- Penrice-Randal, Rebekah
- Cowton, Vanessa M.
- Furnon, Wilhelm
- Harvey, William T.
- Kugathasan, Ruthiran
- Frise, Rebecca
- Baillon, Laury
- Lassaunière, Ria
- Thakur, Nazia
- Gallo, Giulia
- Goldswain, Hannah
- Donovan-Banfield, I'ah
- Dong, Xiaofeng
- Randle, Nadine P.
- Quantrill, Jessica L.
- McKay, Paul F.
- Patel, Arvind H.
- Palmarini, Massimo
- Hiscox, Julian A.
- Bailey, Dalan
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 38
- Issue
- 6
- Pages
- 110344
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC8768428
- OpenAlex
- W4206586685
- Cited by
- 64
- References
- 57
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 11 · 2023: 16 · 2022: 19
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Food and Drug Administration (5F40120C00085, MC_UU12014/2)
- Public Health England (SARS-CoV-2/hu/DK/CL-5/1)
- BBSRC (BBS/E/I/00007038)
- Wellcome Trust (206369/Z/17/Z)
- Pirbright Institute
- MRC (MR/W005611/1)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Zoonotic diseases and public health
- Keywords
- SARS-CoV-2, mink, ferrets, spike protein mutations, reverse zoonosis, host adaptation, viral fitness, risk assessment, reservoir hosts, viral variants
- MeSH terms
- COVID-19, SARS-CoV-2, Viral Zoonoses, Adaptation, Biological, Animals, Ferrets, Humans, Mink, Mutation, Respiratory System, Genetic Fitness, Pandemics, Spike Glycoprotein, Coronavirus
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