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Large scale outbreaks of infectious respiratory disease have repeatedly plagued the globe over the last 100 years. The scope and strength of the outbreaks are getting worse as pathogenic RNA viruses are rapidly evolving and highly evasive to vaccines and anti-viral drugs. Germicidal UV-C is considered as a robust agent to disinfect RNA viruses regardless of their evolution. While genomic damage by UV-C has been known to be associated with viral inactivation, the precise relationship between the damage and inactivation remains unsettled as genomic damage has been analyzed in small areas, typically under 0.5 kb. In this study, we assessed genomic damage by the reduced efficiency of reverse transcription of regions of up to 7.2 kb. Our data seem to indicate that genomic damage was directly proportional to the size of the genome, and a single hit of damage was sufficient for inactivation of RNA viruses. The high efficacy of UV-C is already effectively adopted to inactivate airborne RNA viruses. • RNA viruses are highly sensitive to UV-C as they are inactivated by a single hit of genomic damage. • Viral inactivation rate of RNA viruses seems directly proportional to their genome size. [ABSTRACT FROM AUTHOR]