Exploring coronavirus cell entry with functional viromics

Over the past 2 decades, viral discovery has uncovered thousands of novel coronaviruses in wildlife, including viruses with high similarity to known human pathogens. As human coronaviruses emerge from cross-species transmission events involving wildlife and humans, their frequent discovery in wildlife suggests these viruses will continue to impact global health. Unfortunately, while viruses are discovered often, laboratory limitations have stymied research on experimentally assessing their zoonotic potential. Thus, new laboratory approaches and research mindsets are needed to functionally characterize the ever-growing virome. Here, we discuss several platforms we have developed and the resulting advancements made toward functionally annotating the virome, which we refer to collectively as "functional viromics." We also explore how these approaches may be adapted to assess other viral phenotypes and how laboratory-derived data sets on viral functions will improve next-generation models of zoonotic risk.