RT Journal Article SR Electronic T1 Evidence for a Potential Pre-Pandemic SARS-like Coronavirus Among Animals in North America JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.12.17.473265 DO 10.1101/2021.12.17.473265 A1 Trevor J. Hancock A1 Peyton Hickman A1 Niloo Kazerooni A1 Melissa Kennedy A1 Stephen A. Kania A1 Michelle Dennis A1 Nicole Szafranski A1 Richard Gerhold A1 Chunlei Su A1 Tom Masi A1 Stephen Smith A1 Tim E. Sparer YR 2021 UL http://biorxiv.org/content/early/2021/12/20/2021.12.17.473265.abstract AB In late 2019, a novel coronavirus began circulating within humans in central China. It was designated SARS-CoV-2 because of its genetic similarities to the 2003 SARS coronavirus (SARS-CoV). Now that SARS-CoV-2 has spread worldwide, there is a risk of it establishing new animal reservoirs and recombination with native circulating coronaviruses. To screen local animal populations in the United States for exposure to SARS-like coronaviruses, we developed a serological assay using the receptor binding domain (RBD) from SARS-CoV-2. SARS-CoV-2’s RBD differs from common human and animal coronaviruses allowing us to identify animals previously infected with SARS-CoV or SARS-CoV-2. Using an indirect ELISA for SARS-CoV-2’s RBD, we screened serum from wild and domestic animals for the presence of antibodies against SARS-CoV-2’s RBD. Surprisingly pre-pandemic feline serum samples submitted to the University of Tennessee Veterinary Hospital were ∼70% positive for anti-SARS RBD antibodies. This was independent of prior infection with a feline coronavirus (FCoV), eliminating the possibility of FCoV cross-reactivity. We also identified several white-tailed deer from South Carolina that were also positive for anti-SARS-CoV-2 antibodies. These results bring up an intriguing possibility of a circulating agent (likely a coronavirus) with enough similarity to the SARS RBD to generate cross-reactive antibodies. Finding seropositive cats and white-tailed deer prior to the current SARS-CoV-2 pandemic, further highlights our lack of information about circulating coronaviruses in other species.