The virus causing COVID-19 has been detected in a number of free-ranging and captive animal species. The alarming findings of SARS-CoV-2 circulation in free ranging deer, cryptic circulation of possible animal-associated variant lineages based on NYC sewage surveillance, and canine alphacoronavirus infections in humans highlight a critical need to survey animal populations in the US to understand the risks to those species and also for recombination and spillback to humans. While some groups are performing surveillance for SARS-CoV-2 in wildlife, no system is in place to fully assess the risks using functional characterization. In general, no large-scale pathogen discovery work has been conducted in North America; studies on other continents have largely focused on bats. While bats are a well-known reservoir for coronavirus (CoV) emergence, the potential risks for other mammals are very poorly understood. Assessing the potential of US wildlife species as pathogen reservoirs is vastly under-explored and is essential to prepare for future emerging threats. Our focus here will be on α and β CoV discovery from NE US samples because of the “hotspot” potential of this area. For comparison, we will test recently confirmed CoV positive civet cat and shrew samples from Central Africa as part of a new collaboration between PEH faculty and Labyrinth Global Health, a multicultural organization committed to sustainable scientific engagement. We will use novel sequences from this field surveillance as preliminary data for proposals to NIH and NSF for large-scale projects involving risk assessment of NE wildlife, as well as CoVs from East and Central Africa. Our methods are comprehensive, spanning molecular evolution analysis, ecological modeling, forward evolutionary simulation, molecular docking, and lab studies of viral binding and cell fusion with human receptors.