In vivo anti-papillomavirus activity of nucleoside analogues including cidofovir on CRPV-induced rabbit papillomas.
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.
Christensen
N D
ND
The Jake Gittlen Cancer Research Institute, Department of Pathology, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, USA. ndc1@psu.edu
Pickel
M D
MD
Budgeon
L R
LR
Kreider
J W
JW
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D000077404:Cidofovir; D012777:Cottontail rabbit papillomavirus / Q000187:drug effects / Q000472:pathogenicity; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D009705:Nucleosides / Q000737:chemistry / Q000627:therapeutic use; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D010212:Papilloma / Q000188:drug therapy* / Q000821:virology; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000821:virology; D011817:Rabbits; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000188:drug therapy
D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir