A genus-specific nsp12 region impacts polymerase assembly in Alpha- and Gammacoronaviruses

Abstract

AbstractCoronavirus relevancy for human health has surged over the past 20 years as they have a propensity for spillover into humans from animal reservoirs resulting in pandemics such as COVID-19. The diversity within theCoronavirinaesubfamily and high infection frequency in animal species worldwide creates a looming threat that calls for research across all genera within theCoronavirinaesubfamily. We sought to contribute to the limited structural knowledge within theGammacoronavirusgenera and determined the structure of the viral core replication-transcription complex (RTC) from Infectious Bronchitis Virus (IBV) using single-particle cryo-EM. Comparison between our IBV structure with published RTC structures from otherCoronavirinaegenera reveals structural differences across genera. Usingin vitrobiochemical assays, we characterized these differences and revealed their differing involvement in core RTC formation across different genera. Our findings highlight the value of cross-generaCoronavirinaestudies, as they show genera specific features in coronavirus genome replication. A broader knowledge of coronavirus replication will better prepare us for future coronavirus spillovers.