Nigericin is a potent inhibitor of the early stage of vaccinia virus replication.
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.
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Chad
C
Myskiw
Jessica
J
Piper
Rhiannon
R
Huzarewich
Tim F
TF
Booth
Jingxin
J
Cao
Runtao
R
He
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D023482:Bioterrorism / Q000517:prevention & control; D002264:Carboxylic Acids / Q000494:pharmacology / Q000627:therapeutic use; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000032:analysis; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009550:Nigericin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D011213:Poxviridae Infections / Q000188:drug therapy* / Q000821:virology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D002264:Carboxylic Acids; D049452:Green Fluorescent Proteins; D009550:Nigericin