Human cytomegalovirus (CMV) is the leading non-genetic cause of congenital malformation in developed countries. Despite the clinical importance of congenital CMV, there is currently no therapeutic available for use during pregnancy primarily due to drug toxicity and limited evidence for antiviral efficacy. A number of new experimental anti-CMV compounds (maribavir, letermovir, brincidofovir) are currently undergoing clinical trials in transplant recipients and display high safety and efficacy profiles, but have yet to be investigated in pregnancy. We examined the safety and efficacy profiles of these experimental compounds in the placental TEV-1 trophoblast cell culture model using qPCR and western blot analyses. Treatment of TEV-1 cells with up to 25µM of maribavir, letermovir or cidofovir (the active form of brincidofovir) was well tolerated with no toxic effects observed. Infection of the TEV-1 cells with CMV at a multiplicity of infection of 1 pfu/cell and subsequently treated with 25µM of maribavir, letermovir or cidofovir resulted in significant inhibition of virus progeny production 7 days post infection relative to untreated cells (97.1%, 94.3% and 99.4% inhibition respectively; p<0.05). Furthermore, antiviral treatment similarly inhibited intracellular expression of immediate-early, early and true late viral proteins at 7 days post infection. These data suggest the current experimental anti-CMV compounds may be a viable and effective therapeutic for use during pregnancy. We are currently investigating the use of these compounds in our established human placental explant histoculture model to better inform future directions in clinical trials.