Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine for the treatment of murine cytomegalovirus infection in severe combined immunodeficiency mice.
Mice with severe combined immunodeficiency (SCID) inoculated intraperitoneally with murine cytomegalovirus (MCMV) develop a wasting syndrome at 3-4 days and die at 6-9 days after the infection. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir) and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) were compared for their efficacy against MCMV-induced disease and mortality in SCID mice. Under all treatment conditions, i.e., administration of the test compounds for 5 consecutive days starting on the day of infection (day 0), for 5 consecutive days starting on day 4 after the infection, 2 periods of 3 consecutive days starting on day 0 and day 9 after infection, or as a single dose on day 3 before infection, HPMPC proved far superior to ganciclovir in delaying the onset of the disease and increasing the lifespan of the MCMV-infected mice.
Neyts
J
J
Rega Institute for Medical Research, Leuven, Belgium.
Balzarini
J
J
Naesens
L
L
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D000077404:Cidofovir; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000401:mortality; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir