Letermovir

Letermovir (AIC246) is a potent inhibitor of CMV, which targets the viral terminase complex and remains active against virus resistant to DNA polymerase inhibitors. In Vitro: AIC246 has consistent antiviral efficacy, and there is remarkable selectivity of AIC246 for human cytomegaloviruses^[1]. AD169 mutant strains and designated rAIC246-1 and rAIC246-2 are highly resistant to Letermovir (AIC246), with EC₅₀s of 5.6 nM, 1.24 μM, 0.37 μM, respectively. Letermovir inhibits HCMV replication through a specific antiviral mechanism that involves the viral gene product UL56. Letermovir inhibits HCMV replication in cell culture by interfering with the proper cleavage/packaging of HCMV progeny DNA^[2]. Letermovir inhibits the current gold standard GCV by more than 400-fold with respect to EC₅₀s (mean, 4.5 nM versus 2 μM) and by more than 2,000-fold with respect to EC₉₀ values (mean, 6.1 nM versus 14.5 μM)^[3]. Letermovir in conbination with anti-HCMV drugs causes additive antiviral effects, but there is no interaction between letermovir and anti-HIV drugs^[4]. In Vivo: Letermovir (10-100 mg/kg/day, p.o.) leads to a dose-dependent reduction of the HCMV titer in transplanted cells compared to that of the placebo-treated control group using the mouse xenograft model^[3].