Preliminary Results Indicate the Anti-Proliferative Effect of HIV-1Protease Inhibitors on Trypanosoma brucei Cells can be due to the Non-Specific Targeting of Metallo-and Cysteine-Proteases

Background: Initial studies have confirmed the efficacy of protease inhibitors in the treatment of Trypanosomacruzi, Plasmodium falciparum, and Leishmaniamajor. However, studies on efficacy and specific protease inhibitionof HIV-1 protease inhibitors on Trypanosomabrucei cells remained untouched. The objective of the current studywas to determine the efficacy of two HIV-1 protease inhibitors, ritonavir, and saquinavir, in Trypanosomabruceiproliferation and to determine if these HIV-1 protease inhibitors target the activity of the Trypanosomabruceimajorproteases.Methods: Time dependency test at variable increasing concentrations, motile cell counts, alamarBlue®cellproliferation/viability assay and zymography were among the methods applied.Results: Both ritonavir (IC50=12.23 ± 0.33 μM) and saquinavir (IC50=11.49 ± 0.31 μM) effectively inhibitedTrypanosoma bruceicells proliferation. The major proteases identified in these cells were the cysteine (~29 kDa Mr)and metallo- (~66 kDa Mr) proteases. Protein band densitometry results showed a statistically significant (P-value<0.05) inhibition in metallo-and cysteine-proteases' activity in Trypanosoma brucei cells.Conclusion: The results suggest that RTV and SQV showed an anti-proliferative effect in Trypanosomabruceicells possibly due to the non-specific targeting of the cysteine- and metallo-protease activities of the parasite.