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3-Hydroxyphthaloyl-β-Lactoglobulin. II. Anti-Human Immunodeficiency Virus Type 1 Activity in in Vitro Environments Relevant to Prevention of Sexual Transmission of the Virus

It is anticipated that the rate of sexual transmission of viruses could be substantially decreased by the use of topical chemical barrier methods. Chemical modification of bovine (β-lactoglobulin (β-LG), the major protein of whey, led to the generation of a potent inhibitor (designated 3HP-β-LG) of human immunodeficiency virus type 1 (HIV-1) infection which was also active against herpesviruses. Compounds intended for topical application to prevent sexual transmission of viruses need to maintain their antiviral activity at pH <<7, corresponding to an acidic vaginal environment, and in the presence of seminal fluid. Results presented here show that the binding of 3HP-β-LG to the CD4 receptor for HIV, involved in the anti-HIV-1 activity of this compound, decreases with decreasing pH. The presence of seminal fluid also decreased the binding of 3HP-β-LG to CD4 and diminished the inhibitory effect of the compound on CD4-gp120 binding. 3HP-β-LG was shown to bind Zn++, and the inhibitory effect of seminal fluid could be substantially diminished by chelating Zn++ with ethylenediaminetetraacetate. Saliva had no effect on 3HP-β-LG binding to CD4 or on its interference with gp120-CD4 binding. The decreased 3HP-β-LG-CD4 binding and the concomitant reduction of gp120-CD4 binding inhibition by 3HP-β-LG at low pH and in the presence of seminal fluid could be compensated for by an increase of the 3HP-β-LG concentration and by adding Zn++ chelators to 3HP-β-LG. These results provide a background for the design of 3HP-β-LG formulations for topical use.