The folate antagonist, methotrexate, is a potent inhibitor of murine and human cytomegalovirus in vitro

Antiviral Res. 1989 Mar;11(2):99-106. doi: 10.1016/0166-3542(89)90012-0.

Abstract

Cytomegalovirus (CMV) is a major source of morbidity for immunocompromised patients, such as AIDS patients. The folic acid antagonists have not been explored as potential antiviral agents against CMV. We examined the effects of methotrexate, compared to acyclovir and ganciclovir, on both murine CMV (MCMV) and human CMV (HCMV) in vitro. Using a plaque assay in mouse embryo cells or human foreskin fibroblasts for MCMV and HCMV respectively, we found that methotrexate, in micromolar concentrations, was a potent inhibitor of both viruses. This effect was due to folic acid antagonism since folinic acid abrogated the antiviral effect of methotrexate, but not ganciclovir. Cellular toxicity due to methotrexate appeared insufficient to account for the antiviral effects. The ability of methotrexate to inhibit CMV in vivo merits exploration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyclovir / analogs & derivatives
  • Acyclovir / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / physiology
  • Embryo, Mammalian
  • Fibroblasts / drug effects
  • Folic Acid Antagonists / pharmacology*
  • Ganciclovir
  • Humans
  • Infant, Newborn
  • Leucovorin / pharmacology
  • Male
  • Methotrexate / pharmacology*
  • Mice
  • Skin
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Folic Acid Antagonists
  • Ganciclovir
  • Leucovorin
  • Acyclovir
  • Methotrexate