Effect of oral treatment with (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA on replication of murine cytomegalovirus (MCMV) or human cytomegalovirus (HCMV) in animal models.
We utilized BALB/c mice infected with murine CMV (MCMV) or severe combined immunodeficient (SCID) mice implanted with human fetal tissue and infected with HCMV to determine the efficacy of (S)-9-[3-hydroxy-2-(phophonomethoxy)propyl]adenine ((S)-HPMPA), hexadecyloxypropyl-(S)-HPMPA (HDP-(S)-HPMPA) or octadecyloxyethyl-(S)-HPMPA (ODE-(S)-HPMPA). In MCMV-infected BALB/c mice, oral HDP-(S)-HPMPA at 30 mg/kg significantly reduced mortality when started 24-48 h post inoculation. In the experimental HCMV infection, oral administration of vehicle or 10mg/kg of (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA was initiated 24h after infection and continued for 28 consecutive days. Cidofovir (CDV), at 20mg/kg given i.p., was used as a positive control. HDP-(S)-HPMPA or ODE-(S)-HPMPA significantly reduced viral replication compared to vehicle-treated mice, while oral (S)-HPMPA was ineffective.
Quenelle
Debra C
DC
University of Alabama School of Medicine, Birmingham, AL, USA. dquenell@uab.edu
Collins
Deborah J
DJ
Pettway
Latisha R
LR
Hartline
Caroll B
CB
Beadle
James R
JR
Wan
W Brad
WB
Hostetler
Karl Y
KY
Kern
Earl R
ER
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D006566:Herpesviridae Infections / Q000188:drug therapy*; D008099:Liver / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D018146:Muromegalovirus / Q000187:drug effects; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis
D000998:Antiviral Agents; D063065:Organophosphonates; C530757:octadecyloxyethyl 9-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D003596:Cytosine; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D000225:Adenine; D000077404:Cidofovir; C524480:hexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenine