In silico screening of potential drug against MDR genes (PfCRT/PfMDR1) responsible for Malaria

Abstract

The increasing availability of drug-resistant Plasmodium falciparum infections is putting a strain on the accessibility of potent, safe and cost-effective anti-malarial treatments, necessitating the development of new anti-malarial drug. Malaria deaths were estimated to be around 409000 in 2019. The present study sets to identify novel antimalarial compounds and the virtual screening study reveals that the designed compounds bind more effectively to Plasmodium falciparum chloroquine resistance transporter (PfCRT) and Plasmodium falciparum Multidrug Resistant1 (PfMDR1) than the known inhibitors. Marvin JS was used to design the chemical structure of the molecules and the molecular docking of 75 designed molecules with PfCRT and PfMDR1 was performed to study the interaction between the small molecule and the proteins. The top docked scoring compounds with the respective proteins were subjected to molecular dynamic simulation to study their interaction stability. The ADME/T (absorption, distribution, metabolism and excretion/toxicity) properties of those molecules were also studied and the majority of the properties was found to be within acceptable ranges. After experimental validation to confirm the findings, the screened molecules could be used as potential anti-malarial drugs.