In vivo anti-papillomavirus activity of nucleoside analogues including cidofovir on CRPV-induced rabbit papillomas

Antiviral Res. 2000 Nov;48(2):131-42. doi: 10.1016/s0166-3542(00)00124-8.

Abstract

A series of nucleoside analogues were tested for in vivo anti-papillomavirus activity using the cottontail rabbit papillomavirus (CRPV) domestic rabbit model. Compounds were delivered either topically, injected into growing papillomas, or delivered subcutaneously at a site remote from the papillomas. Compounds tested included cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] (HPMPC); cyclic HPMPC (cHPMPC); cyclopentenylcytosine (CPE-C); lobucavir [1R(1alpha,2beta,3alpha)]-9-[2, 3-bis(hydroxymethyl)cyclobutyl]guanine; 9-((2-phosphonylmethoxy)propyl)adenine (PMPA); adefovir 9-((2-phosphonylmethoxy)ethyl)adenine(PMEA) and cyclopropyl 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (cyclopropylPMEDAP). Dose response curves and time-course treatments were included for most compounds tested. Strong anti-viral activity was detected using cidofovir and cHPMPC when delivered either topically or by the intralesional route. Complete cures were obtained using 1% (w/v) topical cidofovir at dosing schedules of twice daily for 8 weeks beginning at 4 weeks after CRPV infection, which represents a time when papillomas were clearly visible. Complete cures of large established papillomas were obtained by intralesional injection of 1% cidofovir three times per week for 8 weeks. Topical treatments with adefovir had strong anti-viral activity, cyclopropyl PMEDAP had moderate anti-viral activity, and CPE-C, PMPA and lobucavir showed no effects. These data indicate that certain nucleoside analogues have strong in vivo anti-papillomavirus activity and that the CRPV/rabbit model is a good model for assessing clinical responses of anti-viral treatments for patients with HPV disease.

Publication types

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

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Cidofovir
  • Cottontail rabbit papillomavirus* / drug effects
  • Cottontail rabbit papillomavirus* / pathogenicity
  • Cytosine / analogs & derivatives
  • Cytosine / therapeutic use*
  • Disease Models, Animal
  • Humans
  • Nucleosides / chemistry
  • Nucleosides / therapeutic use
  • Organophosphonates*
  • Organophosphorus Compounds / therapeutic use*
  • Papilloma / drug therapy*
  • Papilloma / virology
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / virology
  • Rabbits
  • Treatment Outcome
  • Tumor Virus Infections / diagnosis
  • Tumor Virus Infections / drug therapy

Substances

  • Antiviral Agents
  • Nucleosides
  • Organophosphonates
  • Organophosphorus Compounds
  • Cytosine
  • Cidofovir