SP-303, a natural plant flavonoid polymer of molecular weight 2,100 daltons, was found to have antiviral activity against two strains of type 1 herpes-type simplex virus, including a thymidine-kinase-deficient strain, and a strain of type 2 herpes simplex virus. The 50% effective concentrations (EC50s) were 1-2 μM. Acyclovir, which was run in parallel, had values of 4-28 μM. Surprisingly, the compound was inactive against human cytomegalovirus. SP-303 was also virucidal at 50 μM. Interferon was not induced. The mode of antiviral action of this bio-polymer was through inhibition of virus penetration into cells (EC50 = 2.1 ± 0.2 μM). SP-303 also significantly reduced lesion formation in a mouse vaginal model when applied topically at 5-10%.