title: Efficacy of therapeutic intervention with an oral ether-lipid analogue of cidofovir (CMX001) in a lethal mousepox model.
abstract: In the 21st century we are faced with the potential use of natural or recombinant VARV and MPXV as biological weapons, and the emergence of human MPXV. Such an occurrences would require therapeutic and prophylactic intervention with antivirals. Cidofovir, an antiviral approved for the treatment of cytomegalovirus retinitis in AIDS patients, has activity against poxviruses, but must be administered intravenously and is associated with nephrotoxicity. An ether-lipid analogue of CDV, CMX001 (HDP-CDV), has potent antiviral activity against a range of DNA viruses including poxviruses, excellent oral bioavailability and minimal nephrotoxicity. CMX001 and CDV are equally efficacious at protecting mice from mortality following high ectromelia virus doses (10,000 x LD(50)) introduced by the intra-nasal route or small particle aerosol. Using CMX001 at a 10mg/kg dose followed by 2.5mg/kg doses every other-day for 14 days provided solid protection against mortality and weight loss following an intra-nasal challenge of (100-200) x LD(50) of ectromelia virus. Furthermore, complete protection against mortality was achieved when administration was delayed until as late as 5 days post-infection, which is 3-4 days prior to the death of the untreated controls. This therapeutic window would be equivalent to intervening during the rash stage of ordinary smallpox.
authors: Department of Molecular Microbiology and Immunology, Saint Louis University Medical School, MO 63104, USA.
authors: Scott
authors: S
authors: Parker
authors: Erin
authors: E
authors: Touchette
authors: Christina
authors: C
authors: Oberle
authors: Merrick
authors: M
authors: Almond
authors: Alice
authors: A
authors: Robertson
authors: Lawrence C
authors: LC
authors: Trost
authors: Bernhard
authors: B
authors: Lampert
authors: George
authors: G
authors: Painter
authors: R Mark
authors: RM
authors: Buller
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D004481:Ectromelia virus / Q000187:drug effects*; D004482:Ectromelia, Infectious / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D004986:Ether; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008805:Mice, Inbred A; D063065:Organophosphonates / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D004986:Ether; C525733:brincidofovir; D003596:Cytosine; D000077404:Cidofovir