Subspecies of SARS-CoV-2 from farmed minks might be a threat to humans

Priorities for research to investigate the animal source were discussed by the Office International des Epizooties (OIE) ad hoc Group on COVID-19 at the Human-Animal Interface, and were presented at the WHO Global Research and Innovation Forum (11-12 February 2020) by the President of the OIE Wildlife Working Group (1). Cats (domestic and large cats), mink, and dogs have tested positive for SARS-CoV-2 in the field setting, following contact with humans known or suspected to be infected with SARS-CoV-2 (1,2,3,4,5). In the field setting cats have shown clinical signs of disease including respiratory and gastro-intestinal signs (2). SARS-CoV-2 infection in farmed mink has been characterized by respiratory disease and an increased mortality rate (4).

There is no evidence that companion animals are playing an epidemiological role in the spread of human infections with SARS-CoV-2. However, reports from infected mink farms suggest that in these environments there is the possibility for transmission of SARS-CoV-2 from mink to humans (1,4). Studies are underway to better understand the susceptibility of different animal species to SARS-CoV-2 and to assess infection dynamics in susceptible animal species.

Mustelidae animals such as mink and ferrets can be infected with SARS-CoV-2 relatively easily compared to other mammals. It is not clear why SARS-CoV-2 is so contagious to these animals. Structural remodeling suggested that the G354H substitution in five key amino acid residues in the surface motif of mink ACE2 increased the binding affinity of the RBD of SARS-CoV-2 in comparison with the affinity of human ACE2 for the spike glycoprotein of SARS-CoV-2 (6). As the binding free energy decreases, the affinity between ligand and receptor increases. It is clear that when SARS-CoV-2 is infected with farmed minks that is kept in large quantities in a high density environment, SARS-CoV-2 proliferates in large quantities in the mink body (4,7). As a result, humans may pose a high risk of infection with SARS-CoV-2 as well as farmed minks.

Natural selection “adaptation” in the coronavirus can occur during coronavirus amplification in farmed mink body. Natural selection in such viruses is observed by the appearance of mutations in SARS-CoV-2 that are not observed during the growth process in humans. Mutation of these SARS-CoV-2 is caused by the proliferation likely natural selection process of SARS-CoV-2 in the framed mink body (7).

If these SARS-CoV-2 mutations also have a negative effect on humans (i.e. infection results, high pathogenicity or increased transmission), it is important to note that SARS-CoV-2 is naturally selected during human infection with mutants of SARS-CoV-2.

To date, subspecies of SARS-CoV-2 that occur in the farmed mink body have not been found to infect humans through a chain of natural infections. Mutants of SARS-CoV-2 from farmed minks possibly increase the risk of further infection in humans.

These situations provide compelling scientific evidence that mutants of SARS-CoV-2 from farmed minks might be a threat to humans.

References
1.https://www.oie.int/scientific-expertise/specific-information-and-recommendations/questions-and-answers-on-2019novel-coronavirus/
2. 2 Cats in NY become the first US pets to test positive for virus. AP News. April 22, 2020 (https://apnews com/ 37328ab8db093b8346e26e1840b48af8).
3. Daly N. Seven more big cats test positive for coronavirus at Bronx Zoo. National Geographic 2020 April 22. https://www.nationalgeographic.com/animals/2020/04/tiger-coronavirus-covid19-positive-test-bronx-zoo/
4. Enserink M. Coronavirus rips through Dutch mink farms, triggering culls. Science 2020 Jun 12; 368 (6496):1169. doi: 10.1126/science.368.6496.1169.
5. Sit THC, Brackman CJ, Ip SM, Tam KWS, Law PYT, To EMW, Yu VYT, Sims LD, Tsang DNC, Chu DKW, Perera RAPM, Poon LLM, Peiris M. Infection of dogs with SARS-CoV-2. Nature. 2020 May 14. doi: 10.1038/s41586-020-2334-5.
6. Hayashi T, Abiko K, Mandai M, Yaegashi N, Konishi I. Highly conserved binding region of ACE2 as a receptor for SARS-CoV-2 between humans and mammals. Vet Q. 2020 Dec;40(1):243-249. doi: 10.1080/01652176.2020.1823522.
7. Oude Munnink BB, Sikkema RS, Nieuwenhuijse DF, Molenaar RJ, Munger M. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science 10 Nov 2020: eabe5901 DOI: 10.1126/science.abe5901　　　　　　　　　　　　　　　　　　　　Science  Published on November by Kyoto@Takuma H