3-HYDROXYPHTHALOYL-BETA-LACTOGLOBULIN .2. ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITY IN IN-VITRO ENVIRONMENTS RELEVANT TO PREVENTIONOF SEXUAL TRANSMISSION OF THE VIRUS

It is anticipated that the rate of sexual transmission of viruses coul d be substantially decreased by the use of topical chemical barrier me thods. Chemical modification of bovine beta-lactoglobulin (beta-LG), t he major protein of whey, led to the generation of a potent inhibitor (designated 3HP-beta-LG) of human immunodeficiency virus type 1 (HIV-1 ) infection which was also active against herpesviruses. Compounds int ended for topical application to prevent sexual transmission of viruse s need to maintain their antiviral activity at pH much less than 7, co rresponding to on acidic vaginal environment, and in the presence of s eminal fluid. Results presented here show that the binding of 3HP-beta -LG to the CD4 receptor for HIV, involved in the anti-HIV-1 activity o f this compound, decreases with decreasing pH. The presence of seminal fluid also decreased the binding of 3HP-beta-LG to CD4 and diminished the inhibitory effect of the compound on CD4-gp120 binding. 3HP-beta- LG was shown to bind Zn++, and the inhibitory effect of seminal fluid could be substantially diminished by chelating Zn++ with ethylenediami netetraacetate. Saliva had no effect on 3HP-beta-LG binding to CD4 or on its interference with gp120-CD4 binding. The decreased 3HP-beta-LG- CD4 binding and the concomitant reduction of gp120-CD4 binding inhibit ion by 3HP-beta-LG at low pH and in the presence of seminal fluid coul d be compensated for by an increase of the 3HP-beta-LG concentration a nd by adding Zn++ chelators to 3HP-beta-LG. These results provide a ba ckground for the design of 3HP-beta-LG formulations for topical use.