The effect of the drug, Nelfinavir, an approved HIV protease inhibitor, is shown for three different classes of proteases and two, whole-protein substrates. The inset ESR_SL spectrum reflects both digested and undigested protein, with the sharp lines reflective of low molecular weight or “Mobile” fragments released by digestion of the whole protein. Presented are the fractional changes relative to the no – Nelfinavir control in the “Mobile” population following a 40-min digestion. The drug inhibits the proteolytic activity of pepsin, an aspartyl protease, in-class with HIV protease. In contrast, Nelfinavir promotes proteolysis by cysteinyl (papain) and serinyl (trypsin) proteases. The promotion effect is most pronounced for the whole-protein substrate, serum albumin.