A review of compounds exhibiting anti-orthopoxvirus activity in animal models

Antiviral Res. 2003 Jan;57(1-2):41-52. doi: 10.1016/s0166-3542(02)00199-7.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Bioterrorism / prevention & control
  • Cidofovir
  • Cytosine / analogs & derivatives*
  • Cytosine / therapeutic use*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, SCID
  • Nucleosides / therapeutic use*
  • Organophosphonates*
  • Organophosphorus Compounds / therapeutic use*
  • Orthopoxvirus / drug effects
  • Poxviridae Infections / drug therapy*
  • Poxviridae Infections / virology
  • Rabbits
  • Smallpox / drug therapy
  • Smallpox / virology
  • Thiosemicarbazones / therapeutic use*

Substances

  • Antiviral Agents
  • Nucleosides
  • Organophosphonates
  • Organophosphorus Compounds
  • Thiosemicarbazones
  • Cytosine
  • Cidofovir