METHOTREXATE POTENTIATES ANTI-HERPES SIMPLEX VIRUS TYPE-1 ACTIVITY OF E-5-(2-BROMOVINYL)-2'-DEOXYURIDINE

The pharmacologic of induction of low level of deoxyribanucleoside triphosphates (dNTP) is a novel approach to combined inhibition of virus replication. In accordance with this concept the alteration of antiherpes activity of E-5-(2-bromovinyl-2'-deoxyuridine (BVDU) in combination with methotrexate (MTX), an inhibitor which lowers the intracellular pool of thymidine triphosphate (dTTP) was studied. MTX applied alone at non-toxic concentrations had a moderate effect on herpes simplex virus type 1 (HSV-1) replication in human embryonic skin-muscle fibroblasts. The combination of BVDU and MTX acts synergistically, as measured by virus yield assay in the above mentioned system. The potentiating effect of MTX on the anti-HSV-1 activity of BVDU was reversed by thymidine (dThd).