HCMV (human cytomegalovirus) infection has remained a significant complication during pregnancy and in clinical situations associated with inefficient immunocompetence, such as organ or bone marrow transplantation, cancer, and AIDS. Letermovir inhibits HCMV laboratory strains, clinical isolates, and virus variants resistant to approved drugs with 50% effective concentrations (EC50s) in the low nanomolar range[3]. AIC246 (∼10× the EC50) exerted a marked inhibitory effect on the de novo synthesis of progeny HCMV DNA. AIC246 inhibited the formation of the ∼4-kb terminal fragment in a concentration-dependent manner, indicating that the drug allowed the accumulation of viral concatemeric DNA while further maturation to mature unit-length genomes was prevented. Importantly, C capsids (and consequently C capsid-derived A capsids) were markedly reduced after AIC246 treatment[4].
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