ANTIVIRAL DRUG SUSCEPTIBILITY OF HUMAN-HERPESVIRUS-8

We studied the susceptibility of human herpesvirus 8 (HHV-8) to a numb er 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 mu M, respectively. Ade fovir, an ANP with both antiretrovirus and antiherpesvirus activity, b locked HHV-8 DNA replication at a fourfold-lower concentration than di d foscarnet (EC50 of 39 and 177 mu M, respectively). The most potent i nhibitory effect was obtained with the N-7-substituted nucleoside anal og S2242 (EC50, 0.11 mu M). The nucleoside analogs acyclovir, penciclo vir, H2G {(R)-9-[4-hydroxy-2-(hydroxymethyl) butyl]guanine}, and brivu dine had weak to moderate effects (EC50 of greater than or equal to 75 , 43, 42, and 24 mu M, respectively, and EC90 of greater than or equal to 75 mu M), whereas ganciclovir elicited pronounced anti-HHV-8 activ ity (EC50, 8.9 mu M).