Antiviral drug susceptibility of human herpesvirus 8.
We studied the susceptibility of human herpesvirus 8 (HHV-8) to a number of antiherpesvirus agents. The acyclic nucleoside phosphonate (ANP) analogs cidofovir and HPMPA [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)adenine] effected potent inhibition of HHV-8 DNA synthesis, with 50% effective concentrations (EC50) of 6.3 and 0.6 microM, respectively. Adefovir, an ANP with both antiretrovirus and antiherpesvirus activity, blocked HHV-8 DNA replication at a fourfold-lower concentration than did foscarnet (EC50 of 39 and 177 microM, respectively). The most potent inhibitory effect was obtained with the N-7-substituted nucleoside analog S2242 (EC50, 0.11 microM). The nucleoside analogs acyclovir, penciclovir, H2G ((R)-9-[4-hydroxy-2-(hydroxymethyl) butyl]guanine), and brivudine had weak to moderate effects (EC50 of > or =75, 43, 42, and 24 microM, respectively, and EC90 of > or =75 microM), whereas ganciclovir elicited pronounced anti-HHV-8 activity (EC50, 8.9 microM).
Neyts
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. Johan.Neyts@rega.kuleuven.ac.be
De Clercq
E
E
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D000225:Adenine; D000077404:Cidofovir; C106812:adefovir dipivoxil