Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dki168 Stampidine: a selective oculo-genital microbicide

Adenoviruses (ADVs) are causative agents of severe and extremely contagious ocular and genital infec-tions associated with conjunctivitis, genital ulcers and urethritis. Yet, no functional antiviral compounds are currently available against adenoviral infections. We discovered halogen-substituted phenyl phosphoramidate derivatives of stavudine (STV/d4T) as a new class of dual-function anti-human immuno-deficiency virus (HIV) agents with potent and selective anti-ADV activity. The lead compound, stampidine [50-(4-bromophenyl methoxyalaninylphosphate)-20,30-didehydro-30-deoxythymidine], was the most potent non-toxic dual-function antiviral agent. Stampidine displayed remarkable in vitro and in vivo anti-HIV activity against drug-sensitive and drug-resistant HIV strains. Stampidine was non-cytotoxic and non-irritating tomucosalepithelial cells.Severalpreclinicalstudiesconducted thus far,suggest thatstampidine has clinical potential as a dual-function topical agent for the prevention and/or effective treatment of oculo-genital ADV/HIV infections