title: CMX001 potentiates the efficacy of acyclovir in herpes simplex virus infections.
abstract: Although acyclovir (ACV) has proven to be of value in the therapy of certain herpes simplex virus (HSV) infections, there is a need for more effective therapies, particularly for serious infections in neonates and immunocompromised individuals, where resistance to this drug can be problematic. CMX001 is an orally bioavailable lipid conjugate of cidofovir that is substantially less nephrotoxic than the parent drug and has excellent antiviral activity against all the human herpesviruses. This compound retains full antiviral activity against ACV-resistant laboratory and clinical isolates. The combined efficacy of CMX001 and ACV was evaluated in a new real-time PCR combination assay, which demonstrated that the combination synergistically inhibited the replication of HSV in cell culture. This was also confirmed in murine models of HSV infection, where the combined therapy with these two drugs synergistically reduced mortality. These results suggest that CMX001 may be effective in the treatment of ACV-resistant HSV infections and as an adjunct therapy in individuals with suboptimal responses to ACV.
authors.affiliation: University of Alabama at Birmingham, Department of Pediatrics, 128 Children's Harbor Building, 1600 6th Avenue South, Birmingham, AL 35233-1711, USA. mprichard@peds.uab.edu
authors.forename: Mark N
authors.initials: MN
authors.lastname: Prichard
authors.forename: Earl R
authors.initials: ER
authors.lastname: Kern
authors.forename: Caroll B
authors.initials: CB
authors.lastname: Hartline
authors.forename: E Randall
authors.initials: ER
authors.lastname: Lanier
authors.forename: Debra C
authors.initials: DC
authors.lastname: Quenelle
mesh_terms: D000212:Acyclovir / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002478:Cells, Cultured; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D024882:Drug Resistance, Viral; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C525733:brincidofovir; D003596:Cytosine; D000212:Acyclovir