Virtual Screening of Leishmania calpain natural inhibitors: Prediction of 21 molecules with suitable phrmacokinetic profiles to drug prototypes

Leishmaniasis affects about one million people globally every year. This vector-born disease, caused by Leishmania protozoa, has two main clinical forms:cutaneous and visceral leishmaniasis. Despite this widespread impact, currenttherapeutic options are limited, highlighting the urgent need for newleishmanicidal compounds. This study employed an in-silico screeningapproach to identify Leishmania spp. calpain natural inhibitors by means of alarge-scale molecular docking. Generating a Leishmania calpain 3D model weidentified crucial binding sites. A total of 187,119 molecules were analyzed, andthe 200 with the most favorable binding energies (-10.1 kcal/mol to -12.3kcal/mol) were selected for further bioavailability assessment, leading to 21virtual screening hits as potential oral antileishmanial drugs. The priordemonstration of anti-leishmanial activity for ligands such as cocsoline,cocsuline, and WIN-64821 validated the virtual screening process. The findingsstill need to be confirmed within experimental biological systems.