Several animal models using mice (most frequently), rabbits, or monkeys have been used to identify compounds active against
orthopoxvirus infections. The treatment of vaccinia virus
infections has been well studied in models involving
infection of scarified skin or eyes, or resulting from intravenous, intraperitoneal, intracerebral, or intranasal virus inoculation. Cowpox virus has been used in intranasal or
aerosol infection studies to evaluate the treatment of lethal
respiratory infections. Rabbitpox,
monkeypox, and variola viruses have been employed to a lesser extent than the other viruses in
chemotherapy experiments. A review of the literature over the past 50 years has identified a number of compounds effective in treating one or more of these
infections, which include
thiosemicarbazones,
nucleoside and
nucleotide analogs,
interferon,
interferon inducers, and other unrelated compounds. Substances that appear to have the greatest potential as anti-orthopoxvirus agents are the acyclic
nucleotides, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (
cidofovir,
HPMPC) and 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]
cytosine (
cyclic HPMPC), and the acyclic
nucleoside analog, 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]
purine (
S2242). Other classes of compounds that have not been sufficiently studied in lethal
infection models and deserve further consideration are
thiosemicarbazones related to
methisazone, and analogs of adenosine-N(1)-oxide and 1-(benzyloxy)adenosine.