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A review of compounds exhibiting anti-orthopoxvirus activity in animal models
Donald F Smee1, Robert W Sidwell
1Department of Animal, Dairy and Veterinary Sciences, Institute for Antiviral Research, Utah State University, Logan, UT 84322-5600, USA. dsmee@cc.usu.edu
Abstract:
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.
Insights
This review identifies promising antiviral compounds for orthopoxvirus infections, including acyclic nucleotides like cidofovir and novel nucleoside analogs. Further research into thiosemicarbazones and adenosine analogs is recommended for effective treatments.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- Orthopoxvirus infections pose significant health risks, necessitating effective antiviral therapies.
- Animal models are crucial for evaluating the efficacy of potential treatments against various orthopoxviruses.
Purpose of the Study:
- To review and identify compounds with demonstrated activity against orthopoxvirus infections over the past 50 years.
- To highlight promising antiviral agents and suggest areas for future research.
Main Methods:
- Comprehensive literature review of studies utilizing animal models (mice, rabbits, monkeys) for orthopoxvirus chemotherapy.
- Analysis of compounds tested against vaccinia, cowpox, rabbitpox, monkeypox, and variola viruses.
Main Results:
- Several compound classes show efficacy, including thiosemicarbazones, nucleoside/nucleotide analogs, and interferons.
- Acyclic nucleotides (cidofovir, cyclic HPMPC) and acyclic nucleoside analog S2242 show significant potential.
- Thiosemicarbazones, adenosine-N(1)-oxide, and 1-(benzyloxy)adenosine analogs warrant further investigation in lethal infection models.
Conclusions:
- Acyclic nucleotides and specific nucleoside analogs represent the most promising antiviral agents against orthopoxviruses.
- Further research into thiosemicarbazones and adenosine analogs is needed for developing novel treatments for severe orthopoxvirus infections.
