Investigational Antiviral Therapy Models for the Prevention and Treatment of Congenital Cytomegalovirus Infection during Pregnancy

Antimicrob Agents Chemother. 2020 Dec 16;65(1):e01627-20. doi: 10.1128/AAC.01627-20. Print 2020 Dec 16.


Congenital cytomegalovirus (HCMV) infection may cause significant fetal malformation, lifelong disease, and, in severe cases, fetal or neonatal death. Placental infection with HCMV is the major mechanism of mother-to-child transmission (MTCT) and fetal injury. Thus, any pharmaceutical antiviral interference to reduce viral load may reduce placental damage, MTCT, and fetal disease. However, there is currently no licensed HCMV antiviral for use during pregnancy. In this study, aciclovir and the HCMV-specific antivirals letermovir, maribavir, and cidofovir were compared with ganciclovir for antiviral effects in model systems of pregnancy, including first-trimester TEV-1 trophoblast cell cultures and third-trimester ex vivo placental explant histocultures. HCMV-infected trophoblasts at 7 days postinfection (dpi) showed an EC50 of 21 μM for aciclovir, 0.0007 μM for letermovir, 0.11 μM for maribavir, and 0.29 μM for cidofovir, relative to 0.42 μM for ganciclovir. Antivirals added at 10 μM showed no cytotoxic effects and did not affect trophoblast cell proliferation (P > 0.9999). Multiple-round HCMV replication measured at 7 dpi showed letermovir, maribavir, and cidofovir treatment inhibited immediate early, early, and true late viral protein expression as assayed on Western blots. Antiviral treatment of HCMV-infected placental explants showed significant inhibition (P < 0.05) of viral replication with letermovir (83.3%), maribavir (83.6%), cidofovir (89.3%), and ganciclovir (82.4%), but not aciclovir (P > 0.9999). In ex vivo model systems, recently trialed HCMV antivirals letermovir and maribavir were effective at inhibiting HCMV replication. They partly fulfil requirements for use as safe and effective therapeutics during pregnancy to control congenital HCMV. Clinical trials of these newer agents would assist assessment of their utility in pregnancy.

Keywords: antiviral drugs; cidofovir; congenital infection; cytomegalovirus; ex vivo models; letermovir; maribavir; placenta; pregnancy; valaciclovir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • Child
  • Cytomegalovirus
  • Cytomegalovirus Infections* / drug therapy
  • Female
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical
  • Placenta
  • Pregnancy
  • Virus Replication


  • Antiviral Agents