Mechanism of action of the antiherpesvirus biflavone ginkgetin

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Abstract
Screening of plant extracts found that a biflavone from Cephalotaxus drupacea, which was found to be ginkgetin, is active against herpes simplex virus type 1 (HSV-1). This compound caused dose-dependent inhibition of virus replication with a 50% cytotoxic activity at 12.8 micrograms/ml and 50% anti-HSV-1 activity at 0.91 micrograms/ml, the therapeutic index being 14.1. Ginkgetin also showed inhibitory effects against HSV type 2 and human cytomegalovirus with therapeutic indices of 13.8 and 11.6, respectively. Ginkgetin had a weak virucidal activity against HSV-1 at more than 5 micrograms/ml. Both adsorption of HSV-1 to host cells and virus penetration into cells were unaffected by this agent. Ginkgetin suppressed viral protein synthesis when added at various steps of HSV-1 replication and exerted strong inhibition of transcription of the immediate-early genes.