Effect of Serine Protease Inhibitor, N-α-Tosyl-L-lysyl-Chloromethyl Ketone (TLCK), on Cell-Mediated and Cell-Free HIV-1 Spread

The effect of a serine protease inhibitor, N-α-tosyl-L-lysyl-chloromethyl ketone (TLCK), on cell adhesion and resulting cell-to-cell HIV-1 transmission was examined. Cell-mediated vital spread was blocked by 10-4M TLCK—the nontoxic dose at which the maximum inhibition of cell adhesion was achieved. TLCK (10-4-10-8M range) exhibited a similar dose-dependent effect when tested against cell-free virus infection. These findings suggest that TLCK acts by preventing both cell-cell adhesion and viral binding to the target cell. The effect of TLCK could be attributed to an irreversible modification of surface and/or intracellular proteases required for functional activation of HIV-1 envelope glycoproteins.