Investigations on In Silico Molecular Modelling Against Falcipain-2 in Search of Potent Anti-Malarial Agents

Abstract

Malaria has been a deadly illness transmitted to people by Anopheles mosquitoes, and it can be prevented in two ways, like averting mosquito bites and using medication to prevent the malaria. The development of resistance to anti-malarial medications has caused the poor patient compliance for the treatment of malaria. Hence, there has been a strong need for the design and identification of new chemical entities acting against novel promising malarial targets. Falcipain-2, a cysteine protease, has been such novel target for the investigation of anti-malarial drugs being involved in heme metabolism during the erythrocytic stage. The current state of resistance to malaria treatments has made it imperative to find new antimalarial drugs using in silico tools driven by computer aided drug design. Using AutoDock Vina, 91,001 ligands from the Asinex Elite Synergy 2021-01 library were docked in search of falcipain-2 (PDB ID: 3BPF) inhibitors, which confirmed the discovery of hits (1-20) with superior binding energy than the natural ligand, E64. Moreover, studies for bioavailability and ADMET for better oral bioavailability and druggability have been employed. Further, the dynamics simulation test of the top two hits (1 and 2) were performed through GROMACS 2023.4 for 100 ns, revealing their stability in the docked complex. These findings represent an important start-up in the design and identification of hits against falcipain-2 as anti-malarial agents