PT  - JOURNAL ARTICLE
AU  - Kaitlin Sawatzki
AU  - Nichola Hill
AU  - Wendy Puryear
AU  - Alexa Foss
AU  - Jonathon Stone
AU  - Jonathan Runstadler
TI  - Ferrets not infected by SARS-CoV-2 in a high-exposure domestic setting
AID  - 10.1101/2020.08.21.254995
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.21.254995
4099  - http://biorxiv.org/content/early/2020/08/25/2020.08.21.254995.short
4100  - http://biorxiv.org/content/early/2020/08/25/2020.08.21.254995.full
AB  - Ferrets (Mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to SARS-CoV-2 infection and onward transmission. Here, we report the results of a natural experiment where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic COVID-19. We observed no evidence of SARS-CoV-2 transmission from humans to ferrets based on RT-PCR and ELISA. To better understand this discrepancy in experimental and natural infection in ferrets, we compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein (Spike) mutations associated with mustelids. While we found evidence that ACE2 provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin activity. These data support that host factors interacting with the novel S1/S2 cleavage site may be a barrier in ferret SARS-CoV-2 susceptibility and that domestic ferrets are at low risk of natural infection from currently circulating SARS-CoV-2. This may be overcome in laboratory settings using concentrated viral inoculum, but the effects of ferret host-adaptations require additional investigation.Competing Interest StatementThe authors have declared no competing interest.