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

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.; Lassauniere, 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.

doi:10.1101/2021.08.20.456972

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bioRxiv · 10.1101/2021.08.20.456972

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

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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.

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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., Lassauniere, 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.. 2021-08-20. Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway.. https://doi.org/10.1101/2021.08.20.456972

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