title: Antiviral prophylaxis of smallpox.
abstract: Proof-of-concept studies suggest that current defences against smallpox could be strengthened by supplementing vaccination with antiviral drug prophylaxis, based on aerosolized or orally available forms of the long-acting medication cidofovir. Delivery of aerosolized cidofovir to mice results in its prolonged retention in respiratory tissues and protection against lethal intranasal or aerosol poxviral challenge. Although cidofovir itself is not orally available, the addition of an alkoxyalkanol ether side-chain allows it to be absorbed from the gastrointestinal tract. This also markedly increases its antiviral activity and lengthens its intracellular half-life from roughly 3 to 8-10 days. Oral treatment also protected mice against lethal poxviral challenge. These results suggest that a single aerosol dose of cidofovir (or an alkoxyalkanol-ether derivative) could provide prolonged protection against initiation of smallpox infection, whereas oral treatment could prevent both initiation of infection and internal dissemination of virus. Both approaches may avoid the nephrotoxicity that occasionally results from intravenous cidofovir therapy.
authors.affiliation: Biodefense Clinical Research Branch, Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mbray@niaid.nih.gov
authors.forename: Mike
authors.initials: M
authors.lastname: Bray
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077404:Cidofovir; D003131:Combined Modality Therapy; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D012899:Smallpox / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000627:therapeutic use; D014611:Vaccination
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D012900:Smallpox Vaccine; D003596:Cytosine; D000077404:Cidofovir