Zhou J, Peacock TP, Brown JC, Goldhill DH, Elrefaey AME, Penrice-Randal R, Cowton VM, De Lorenzo G, Furnon W, Harvey WT, Kugathasan R, Frise R, Baillon L, Lassaunière R, Thakur N, Gallo G, Goldswain H, Donovan-Banfield I, Dong X, Rangle NP, Sweeney F, Glynn MC, Quantrill JL, McKay PF, Patel AH, Palmarini M, Hiscox JA, Bailey D, Barclay WS (2021) bioRxiv DOI: 10.1101/2021.08.20.456972 PDF
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.