Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections

Antiviral Res. 2003 Jan;57(1-2):13-23. doi: 10.1016/s0166-3542(02)00196-1.


We assessed the activities of 24 different antiviral compounds against smallpox (two strains of variola major and one of variola minor), monkeypox, vaccinia and cowpox viruses by a neutral red uptake assay. To establish assay parameters, we examined viral replication and its inhibition at various times postinfection and at several multiplicities of infection. Drugs were selected to target a range of functions involved in viral replication. Eight compounds (cidofovir, cyclic HPMPC (cHPMPC), HPMPA, ribavirin, tiazofurin, carbocyclic 3-deazaadenosine, 3-deazaneplanocin A and DFBA (1-(2,4-difluorobenzyloxy)adenosine perchlorate)-a derivative of adenosine N1-oxide) inhibited the replication of all three variola strains and the other orthopoxviruses at drug concentrations within a pharmacologically achievable range. Two others (methisazone and bis-POM-PMEA) showed a lesser degree of antiviral effect, while the remainder were inactive. To examine possible naturally occurring drug resistance among a large number of variola isolates obtained from different geographical regions and at different times, we examined the sensitivity of 35 different strains of variola as well as other orthopoxviruses to a subset of three of the most active compounds: cidofovir, cHPMPC, and ribavirin. Preliminary data indicate that nearly all isolates appear to have similar drug sensitivities. These findings are currently being verified and expanded.

Publication types

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

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Cell Line
  • Chlorocebus aethiops
  • Humans
  • Microbial Sensitivity Tests
  • Monkeypox virus / drug effects*
  • Monkeypox virus / growth & development
  • Neutral Red / metabolism
  • Orthopoxvirus / drug effects*
  • Orthopoxvirus / growth & development
  • Poxviridae Infections / drug therapy
  • Poxviridae Infections / virology*
  • Variola virus / drug effects*
  • Variola virus / growth & development
  • Vero Cells
  • Viral Plaque Assay
  • Virus Replication / drug effects


  • Antiviral Agents
  • Neutral Red