Inhibition of human cytomegalovirus replication by valaciclovir

Vertical transmission of human cytomegalovirus (HCMV) during pregnancy is a major cause of congenital disease. In the absence of robust vaccination strategies, antiviral drug regimens are being developed to inhibit the vertical transmission of the virus. Recent clinical data have indicated that valaciclovir, an orally bioavailable form of aciclovir, was effective at limiting vertical transmission of HCMV when administered during pregnancy. However, there is no widely cited <i>in vitro</i> analysis of valaciclovir's antiviral effect against HCMV, and it is possible, like aciclovir, that valaciclovir has poor anti-HCMV activity. The antiviral effects of aciclovir and valaciclovir against HCMV were compared to the widely used anti-HCMV drug ganciclovir. Compared to ganciclovir, the anti-HCMV effects of either aciclovir or valaciclovir were poor, and robust anti-HCMV activity in all cell lines tested (adult fibroblast, foetal fibroblast or trophoblast cells) was only observed at high drug concentrations. All drugs had no obvious effects on the viability of uninfected cells. Overall, valaciclovir had poor anti-HCMV activity, and its anti-HCMV efficacy upon administration during pregnancy may rely on a combination of factors. These data argue for the continued development of valaciclovir and anti-HCMV compounds to inhibit vertical virus transmission.