A polemic in response to Zhou et al (J Infect Dis 2021;224:415-9.) is given.The author Zhou et al described a concentration-dependent increase in rate of mutation in a modified in vitro Chinese hamster ovary cell hypoxanthine phosphorybosyl transferase assay with N-hydroxycytidine.The author in contrast, we have conducted a more comprehensive series of in vitro and in vivo genotoxicity studies, which, based on the totality of the data, demonstrate a low risk for genotoxicity with MOV in clin. use.It is important to note that the assay conditions used by Zhou et al for their in vitro HPRT assay differed significantly from standard protocols conducted under regulatory test guidelines.The mutation results provided by Zhou et al were reported as total mutant colonies rather than mutant frequency, which does not allow for comparison of neg. and pos. control data to publicly available literature.The rationale for the NHC concentrations used in the assay (or concurrent control compounds) was not provided.Finally, information regarding the origin and purity of the NHC material used was not provided, and it is uncertain whether the stability or impurity of the material was characterized.The author concluded that comprehensive safety evaluation coupled with the preclin. antiviral efficacy and clin. experience to date support the ongoing studies of MOV in patients, including those most likely to benefit from early intervention.