Amprenavir-Ritonavir Combination Is More Effective in Leishmania donovani Compared to Leishmania major

Leishmaniasis is an infectious disease caused by unicellular protozoan parasite Leishmania. The disease is transmitted to humans through infected female Phlebotomus sand flies, which feed on blood. People belonging to low socioeconomic status are generally more prone to Leishmania infection, due to their weaker immune system. Ironically, drugs that are in clinical use against leishmaniasis are toxic and very expensive. There is also an increased incidence of resistance against conventional drugs. Due to these reasons, there is a need for development of new drugs for the treatment of leishmaniasis, which is affordable, non-toxic, and effective against those parasites that are resistant to conventional drugs. The antileishmanial activity of HIV-1 protease inhibitors (PIs) is reported. Therefore, the present study focused on the combinational therapy of HIV-1 protease inhibitors, amprenavir (APV) in combination with ritonavir (RTV), against Leishmania donovani and Leishmania major. This combination effectively killed the parasites, which is more potent against L. donovani compared to L. major. The combination of PIs exerted antileishmanial effect by increased ROS generation followed by elevated nitric oxide activation leading to oxidative stress. Therefore, the study might be exploited for the therapeutic development against leishmaniasis as a substitute to replace the conventional drugs.