title: Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone.
abstract: Mitoxantrone, an FDA-approved therapeutic for the treatment of cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against vaccinia virus. To determine whether this activity extends to other orthopoxviruses, mitoxantrone was tested against cowpox and monkeypox. Mitoxantrone demonstrated an EC(50) of 0.25 μM against cowpox and 0.8 μM against monkeypox. Intraperitoneal treatment of cowpox virus-challenged C57Bl/6 mice with 0.5 mg/kg mitoxantrone resulted in 25% survival and a significant increase in survival time. In an effort to improve its efficacy, mitoxantrone was tested for synergistic activity with cidofovir. In vitro tests demonstrated significant synergy between the two drugs against cowpox; however, no synergistic effect on animal survival or median time-to-death was seen in intranasally-infected BALB/c mice. Significantly fewer animals survived when treated with a combination of 0.5 mg/kg mitoxantrone and 100 mg/kg cidofovir than with 100 mg/kg cidofovir alone. This is, to our knowledge, the first report of limited anti-orthopoxvirus activity by mitoxantrone in an animal model.
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: altmannse@niaid.nih.gov.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Altmann
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Smith
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Dyall
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Reed F
authors.initials: RF
authors.lastname: Johnson
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lori E
authors.initials: LE
authors.lastname: Dodd
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Paragas
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Blaney
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015605:Cowpox / Q000188:drug therapy / Q000821:virology*; D015608:Cowpox virus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008942:Mitoxantrone / Q000494:pharmacology*; D045908:Mpox, Monkeypox / Q000188:drug therapy / Q000821:virology*; D008993:Monkeypox virus / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D008942:Mitoxantrone