Dipyridamole Potentiates the Activity of Various Acyclic Nucleoside Phosphonates against Varicella-Zoster Virus, Herpes Simplex Virus and Human Cytomegalovirus

Dypiridamole (DPM) is widely used in the treatment of cardiovascular diseases as a coronary vasodilator and inhibitor of platelet aggregation. Phosphonylmethoxyethyl (PME) and 3-hydroxy-2-phosphonylmethoxypropyl (HPMP) derivatives of purines and pyrimidines are potent and selective inhibitors of varicella-zoster virus (VZV), herpes simplex virus (HSV) and human cytomegalovirus (HCMV). We have found that DPM markedly potentiates the antiviral effects of the PME derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAP), and of the HPMP derivatives of adenine (HPMPA), 3-deazaadenine (HPMPc 3 A) and cyclic HPMPA (cHPMPA). This was reflected by a significant decrease in the 50% inhibitory concentration of the acyclic nucleoside phosphonates for VZV-, HSV- and HCMV-induced cytopathic effect or plaque formation. DPM did not enhance the activity of vidarabine, acyclovir or ganciclovir. These results were confirmed by virus yield assays (for HSV and HCMV) and flow cytometry (for VZV).