Abstract: The emergence of zoonotic pathogenic viruses has accentuated the need to develop broad-spectrum antivirals and vaccines. Highly modular yeast-based phenotypic platforms for characterization and targeting of RNA capping enzymes from emerging pathogens including coronaviruses, MPV, ASFV, and WNV, are disclosed herein. This platform can identify key amino acid residues and protein domains. Inactivation and attenuation mutations in viral enzymes are also disclosed herein. This platform is applied to vertebrate RNA capping enzymes, demonstrating use for high-throughput phenotypic screening. The disclosed platforms are highly modular and can be adapted for RNA capping enzymes from viruses and variants that emerge in the future.