Poxviruses remain a significant public health concern due to their potential use as bioterrorist agents and the spread of animal borne poxviruses, such as monkeypox virus, to humans. Thus, the identification of small molecule inhibitors of poxvirus replication is warranted. Vaccinia virus is the prototypic member of the Orthopoxvirus genus, which also includes variola and monkeypox virus. In this study, we demonstrate that the carboxylic ionophore nigericin is a potent inhibitor of vaccinia virus replication in several human cell lines, in HeLa cells, we found that the 50% inhibitory concentration of nigericin against vaccinia virus was 7.9 nM, with a selectivity index of 1038. We present data demonstrating that nigericin targets vaccinia virus replication at a post-entry stage. While nigericin moderately inhibits both early vaccinia gene transcription and translation, viral DNA replication and intermediate and late gene expression are severely compromised in the presence of nigericin. Our results demonstrate that nigericin has the potential to be further developed into an effective antiviral to treat poxvirus infections.Les poxvirus demeurent une préoccupation importante de santé publique en raison de leur utilisation potentielle comme agents de bioterrorisme et de la propagation des poxvirus dorigine animale, comme lorthopoxvirus simien, aux êtres humains. Ainsi, lidentification de petites molécules inhibitrices de la réplication des poxvirus est justifiée. Le virus de la vaccine est le membre prototype du genre Orthopoxvirus, qui inclut aussi le virus de la variole et lorthopoxvirus simien. Dans cette étude, il est démontré que la nigéricine ionophore carboxylique est un puissant inhibiteur de la réplication du virus de la vaccine dans plusieurs lignées cellulaires humaines, dans les cellules HeLa, il a été constaté que la concentration inhibitrice 50% de la nigéricine contre le virus de la vaccine est de 7,9 nM, avec un indice de sélectivité de 1038. Des données
