Particular characteristics of the anti-human cytomegalovirus activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) in vitro.
The acyclic nucleoside phosphonate analogue (S)-1-[3-hydroxy-2-phosphonylmethoxypropyl]cytosine (HPMPC) is a potent and selective inhibitor of human cytomegalovirus (HCMV) replication and DNA synthesis. Unlike 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), HPMPC inhibits HCMV replication in cell cultures which have been treated with the compound before infection. Upon short-pulse treatment of HCMV-infected cells with HPMPC, a long-lasting antiviral response is obtained. The antiviral activity of HPMPC, unlike the antiviral activity of other cytosine derivatives (i.e. Ara-C, FIAC), is not readily reversed by 2'-deoxycytidine or cytidine. Neutral and alkaline sucrose gradient analysis of HCMV DNA isolated from HPMPC-treated HCMV-infected cell cultures revealed that HPMPC does not cause (detectable) single- or double-strand breakage of HCMV DNA.
Neyts
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Snoeck
R
R
Balzarini
J
J
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003561:Cytarabine / Q000031:analogs & derivatives / Q000494:pharmacology; D003562:Cytidine / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D003841:Deoxycytidine / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D006801:Humans; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003561:Cytarabine; D003841:Deoxycytidine; C026023:fiacitabine; D003562:Cytidine; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir