Abstract
As the COVID-19 pandemic enters its fifth year, research tools to study the SARS-CoV-2 (CoV-2) virus are critical, and many researchers have turned to another beta coronavirus: HCoV-OC43 (OC43). OC43 is a ubiquitous pathogen that now causes a common cold, but its emergence in 1890 closely coincided with and likely produced the catastrophic Russian Flu pandemic. Beyond their historical parallels, OC43 and CoV-2 share similar genetics and disease sequelae. Both viruses induce respiratory symptoms. Additionally, OC43 infection can result in acute neurological dysfunction in children, and exposure to OC43 has been linked to long-term neurological disorders in adults. Similarly, CoV-2 can produce acute neuropathology and the phenomenon of prolonged symptoms known as Long-COVID that typically impacts the brain. Mouse models have been developed to study the pathogenesis of both OC43 and CoV-2, thereby facilitating research on the neurological sequelae associated with either infection. These models have been further utilized to test therapeutic interventions against both viruses, as researchers seek to establish the potential for using OC43 as a proxy for CoV-2. Further, because mouse models of the two betacoronaviruses exhibit neurological sequelae, using OC43 likely could provide insight into the impact of COVID-19 on the brain. OC43 requires a lower biosafety level than CoV-2, which makes it accessible to more researchers resulting in expeditious scientific progress in the ongoing COVID-19 pandemic.