Prevention of Human Immunodeficiency Virus Type 1 Transmission by Pharmaceuticals Targeted to Host Proteins Required for Virus Infection? Consideration of Farnesyl Thiosalicylic Acid, a Ras Inhibitor
Journal of Antivirals & Antiretrovirals
Recent success in defining the human immunodeficiency virus type 1 (HIV-1) -host cell protein interaction network has provided an opportunity for development of novel antiviral therapeutics targeted to host proteins required for virus infection. This expanded earlier successful development of antagonists for the cellular receptors (CD4) and co-receptors (CCR5 or CXCR4) involved in virus attachment. Induction of the G-alpha q signaling cascade by the HIV-1 envelope is required for virus entry,
... d it's blocking prevented HIV-1-mediated membrane fusion and initiation of infection. One of the blockers, the Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS), was reported to interfere with HIV-1 infection. Since FTS appears to have an established safety record and is being evaluated (as Salirasib, oral) in phase II human clinical trials for treatment of lung cancer, it was of interest to evaluate the potential of FTS as a topical microbicide for prevention of sexual transmission of HIV-1. Data shown here indicated that this compound did not meet the criteria of an established screening algorithm for evaluation of topical microbicides. Nevertheless, the possibility remains to be explored that FTS (especially when used in combination with other anti-HIV drugs) might be useful in sustained pre-exposure prophylaxis to prevent HIV-1 transmission. Abbreviations: FTS: S-trans, trans-Farnesyl Thiosalicylic Acid or Farnesyl Thiosalicylic Acid; PBS: Phosphate Buffered Saline; DMSO: Dimethylsulfoxide; CCR5 and CXCR4: Coreceptors for R5 and X4 tropic HIV-1; IC 50 (IC 90 ): Inhibitor Concentrations at which virus replication is reduced to 50% (90%) of that observed in the absence of inhibitor; TC 50 : concentration of a compound at which 50% of cells, in the absence of virus, remain viable.