MOLECULAR TARGETS FOR HUMAN PAPILLOMAVIRUSES - PROSPECTS FOR ANTIVIRAL THERAPY

A substantial medical need exists for the development of antiviral med icines for the treatment of diseases associated with infection by huma n papillomaviruses (HPVs). HPVs are associated with various benign and malignant lesions including benign genital condyloma, common skin war ts, laryngeal papillomas and anogenital cancer. Since treatment option s are limited and typically not very satisfactory, the development of safe and effective antiviral drugs for HPV could have substantial clin ical impact. In the last few years, exciting advances have been made i n our understanding of papillomavirus replication and the effects that the virus has on growth of the host cell. Although still somewhat rud imentary, techniques have been developed for limited virion production in vitro offering the promise of more rapid advances in the dissectio n and understanding of the virus life cycle. Of the 8-10 HPV gene prod ucts that are made during infection, only one encodes enzymatic activi ties, the E1 helicase. Successful antiviral therapies have traditional ly targeted viral enzymes such as polymerases, kinases and proteases. In contrast, macromolecular interactions which mediate the functions o f E6, E7 and E2 are thought to be more difficult targets for small mol ecule therapy.