ACROSIN INHIBITOR, 4'-ACETAMIDOPHENYL 4-GUANIDINOBENZOATE, AN EXPERIMENTAL VAGINAL CONTRACEPTIVE WITH ANTI-HIV ACTIVITY

Serine proteases are involved in a wide variety of seemingly unrelated physiological functions in eluding capacitation of the spermatozoa and potentiation of human immunodeficiency virus (HIV) infection. The experimental vaginal contraceptives derived from 4-guanidinobenzoic acid act through inhibition of acrosin-a serine protease from the sperm. The serial ten-fold dilutions of 4'-acetamidophenyl 4-guanidinobenzoate (AGE) were tasted in vitro for the effect against HIV infection by assaying the suppression of de novo p24 synthesis in virus-inoculated MT-4 T lymphocytes. The results reveal that complete inhibition of HIV occurred at 100 mu g/ml-a dose corresponding to previously reported concentrations responsible for preventing fertilization in rabbits. These findings suggest that serine protease inhibitors and in particular the guanidinobenzoates, reported to be up to 100-fold more potent and less irritating than nonoxynol-9, can be potentially operative against sexual transmission of HIV.