title: Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections.
abstract: 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.
authors.affiliation: Department of Viral Therapeutics, Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA. robert.baker@det.amedd.army.army.mil
authors.forename: Robert O
authors.initials: RO
authors.lastname: Baker
authors.forename: Mike
authors.initials: M
authors.lastname: Bray
authors.forename: John W
authors.initials: JW
authors.lastname: Huggins
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D008826:Microbial Sensitivity Tests; D008993:Monkeypox virus / Q000187:drug effects* / Q000254:growth & development; D009499:Neutral Red / Q000378:metabolism; D018155:Orthopoxvirus / Q000187:drug effects* / Q000254:growth & development; D011213:Poxviridae Infections / Q000188:drug therapy / Q000821:virology*; D012901:Variola virus / Q000187:drug effects* / Q000254:growth & development; D014709:Vero Cells; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D009499:Neutral Red