Inhibitory Effects of Podophyllotoxin Derivatives on Herpes Simplex Virus Replication

Podophyllotoxin and its derivatives were examined for inhibitory effects on the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), including acyclovir-resistant virus and clinical isolates. Deoxypodophyllotoxin (RD4–6266) proved to be a highly potent and selective inhibitor of all HSV strains in MRC-5 cells. EC 50 values of RD4–6283 (in which the methylenedioxy ring A is modified) for HSV-1 and -2 were inferior to those of deoxypodophyllotoxin. However, podorhizol (RD4–6277) and 5′-methoxy-podorhizol (RD4–6276), in which ring C is absent, did notinhibit HSV replication. Moreover, RD4–6266 also inhibited the production of infectious virus particles of HSV-1 KOS strain and HSV-2 G strain. In contrast, none of the podophyllotoxin derivatives were found to have an antiviral effect against influenza A virus, respiratory syncytial virus or human cytomegalovirus in doses not toxic to the cells.