The COVID-19 pandemic also brought notable attention to the zoonotic role for animal coronaviruses that exist in a wide range of companion animals and agricultural species. Indeed, canine coronavirus (CCoV) has recently become flagged as the eighth human coronavirus based on several isolations in humans. CCoV type 2 (CCoV-2) belongs to the Alphacoronavirus-1 species, together with other coronaviruses of veterinary relevance, including feline coronavirus (FCoV), transmissible gastroenteritis virus, and porcine respiratory coronavirus. In addition to these viruses, pigs also harbor a number of additional coronaviruses including porcine epidemic diarrhea virus and porcine deltacoronavirus, and birds harbor a widely disseminated and antigenically heterogenous coronavirus (infectious bronchitis virus) Although frequently documented as a mild gastrointestinal virus in domestic dogs, highly pathogenic mutant variants of CCoV-2 have been documented, as well as several emerging recombinant variants with distinctive spike genes. FCoV-like viruses have also been detected in humans with influenza-like symptoms in the U.S. Interestingly, the S gene of one of the variants was more similar to HCoV-OC43 (a betacoronavirus) than to FCoV-1, suggesting a recombination event between these CoVs. It is also important to note the incidence of enzootic coronaviruses occurring in felids, which may be more substantial than appreciated. For FCoV-1, there is no well documented study of transmission to humans, with the exception of the one study from Arkansas described above, although enzootic coronaviruses do seem to transmit easily between cats and dogs and may readily recombine. Bovine coronavirus (BCoV) now widely considered to be the source of the now-endemic human coronavirus (HCoV-OC43). Molecular clock analysis of HCoV-OC43 dated the common ancestor and presumed spillover event to a period around the turn of the 20th century. In addition to the well-established zoonotic role of bovine coronavirus, horses are infected with an equine coronavirus (ECoV), which is a betacoronavirus related to but distinct from the BCoV now widely considered to be the source of the now-endemic human coronavirus (HCoVOC43). Molecular clock analysis of HCoV-OC43 dated the common ancestor and presumed spillover event to a period around the turn of the 20th century. ECoV is an emerging infection of horses and can cause respiratory disease. Given the precedent of BCoV becoming an endemic human coronavirus and the status of horses as companion animals, ECoV should be considered a plausible pandemic-potential agent.

The Whittaker lab has notable experience with human and animal coronavirus infections and the features of the viral spike protein driving transmission and pathogenesis. This expertise will be used in this project to test novel antivirals in cell culture, within the One Health context described above.