application): Herpes simplex viruses (HSV) establish lifelong latent infections in humans, and recurrent disease, manifested in oral or ocular lesions (HSV1) or in genital lesions (HSV2), may occur in susceptible individuals. Except for prophylactic acyclovir in certain cases, there are no drugs available to prevent recurrences or to prevent asymptomatic viral shedding and infectivity, especially of genital herpes. Among possible viral functions involved in latency, the applicant has established that an inhibitor of the viral thymidine kinase reduces the frequency of reactivation of HSV1 in animal models. The applicant proposes to develop this compound, 9-(4-hydroxybutyl)-N2- phenylguanine (HBPG), and relate N2- phenylguanines for use to prevent recurrent herpes simplex infections in humans. In Phase I the specific aims are: 1. To develop and exploit an efficient synthetic method to produce the drug candidate HBPG, 9-(4-hydroxybutyl)-N2- phenylguanine. 2. To corroborate the efficacy of HBPG to prevent recurrent Herpes simplex virus type 1 infections in mice 3. To demonstrate efficacy of HBPG to prevent recurrent Herpes simplex type 2 infections in guinea pigs. 4. To synthesize second generation anti-recurrence drugs and test their inhibitory potencies against HSV1 and HSV2 thymidine kinases. GLSynthesis Inc. and the University of Massachusetts, holder of the patent covering HBPG and related compounds, will share in licensing and royalty revenues for drugs resulting from this project.
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