Surrogate animal models must be used for testing
antiviral agents against
variola (smallpox) virus
infections. Once developed, these, compounds can be stockpiled for use in the event of a bioterrorist incident involving either
variola or monkeypox virus, or used to treat an occasional serious
orthopoxvirus infection, such as disseminated
vaccinia complication following exposure to the live virus
vaccine. Recently, considerable progress has been made in the discovery of novel
antiviral agents found active against orthopoxviruses in vivo. This includes the development of new animal models or refinement of existing ones for compound efficacy testing. Current mouse models employ
ectromelia,
cowpox and
vaccinia (WR and IHD strains) viruses with respiratory (lung) or tail lesion
infections commonly studied. Rabbitpox and
vaccinia (WR strain) viruses are available for rabbit
infections.
Monkeypox and variola viruses are used for infecting monkeys. This review describes these and other animal models, and covers compounds found active in vivo from 2003 to date.
Cidofovir, known to be active against orthopox
virus infections prior to 2003, has been studied extensively over recent years. New compounds showing promise are orally active inhibitors of
orthopoxvirus infections that include
ether lipid prodrugs of
cidofovir and (
S)-HPMPA,
ST-246,
N-methanocarbathymidine (
N-MCT) and SRI 21950 (a 4'-thio derivative of
iododeoxyuridine). Another compound with high activity but requiring parenteral administration is HPMPO-DAPy. Further development of these compounds is warranted.