May 2020—Each year a growing number of novel viruses are discovered in the wild animal kingdom with the use of next-generation sequencing technology. However, the current method of functionally assessing the zoonotic potential—that is, the potential to be transmitted to humans—of novel viruses involves synthesis of viral genomes (tens of thousands of bases) and reverse genetic engineering to produce a recombinant virus. This is expensive and time-consuming, and it is not practical due to the scale of new viral strains being discovered. To overcome this hurdle, Letko, et al., developed a rapid and cost-effective method that could functionally assess a number of related viruses for zoonotic potential. The essential component of viral cross-species transmission is cell entry, which is a multi-step process involving attachment of the virus to the host cell surface, receptor engagement, processing of host proteases, and downstream membrane fusion.