AEGiS-14IAC: SAMMA is a novel microbicide which inhibits human immunodeficiency virus and herpes simplex virus entry.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

SAMMA is a novel microbicide which inhibits human immunodeficiency virus and herpes simplex virus entry.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrD1314)

Herold B, Bello I, Marcellino M, Dzeuzelewski M, Cheshenko N, Francois F, Casullo VM, Anderson R, Chany C, Zaneveld LJ, Waller DP, Klotman ME
Mt. Sinai School of Medicine, New York, NY, United States

BACKGROUND: Although renewed efforts in vaccine development have provided valuable insight, a protective vaccine may not be available in the near future. Topical microbicides that block the establishment of infection at the mucosal surface provide an additional method of intervention that can be initiated by the individual at risk independent of the sexual partner. Presently marketed vaginal barrier agents are cytotoxic and damage the vaginal epithelium and natural vaginal flora with frequent use. Novel non-cytotoxic agents are needed to protect men and women from sexually transmitted diseases. One novel candidate is a polymer derived from sulfuric acid treatment of mandelic acid or SAMMA.

METHODS: The spectrum of anti-viral activity as well as cytotoxicity of SAMMA was defined using clinical isolates of HIV and HSV and primary cell culture systems including human cervical cells, macrophages and T-cells as well as U87 cells engineered to express single HIV-1 coreceptors. The inhibitory effects of the compound on binding, fusion, entry and post viral entry were defined using viral infection and viral glycoprotein interactions with receptor-expressing cell lines.

RESULTS: SAMMA blocked laboratory adapted and primary isolates of HSV and HIV in primary cells at a dose range of 10-100 ug/ml with no measurable toxicity. The compound efficiently blocked infection with R5 and X4 HIV isolates. It blocked binding of HIV and HSV onto cells as well as binding of their respective glycoproteins gp120 and gB. SAMMA also inhibited HSV entry post-binding and blocked cell-cell spread of virus.

CONCLUSION: SAMMA has broad inhibitory activity against HIV and HSV with little or no cytotoxicity and an excellent selectivity index. It is a novel candidate microbicide that warrants further pre-clinical evaluation.

Keywords: AEGIS, HIV, Simplexvirus, Anti-Infective Agents, HIV-1, HIV Infections, Sexually Transmitted Diseases, HIV Envelope Protein gp120, Anti-Infective Agents, Local, Cell Line, Vagina, Macrophages, Human, Female, Male, immunology

020707
WeOrD1314