Cipargamin could inhibit human adenosine receptor A3 with higher binding affinity than Plasmodium falciparum P-type ATPase4: An In Silico Study

Abstract

This study aimed to predict the molecular targets of cipargamin in human, and estimate the structural dynamics and binding affinity of their interactions. In silico methods which involve target prediction, structure modelling and dynamics and molecular docking were used. The result showed that cipargamin showed 100% probability of binding to human Adenosine A3 receptor (ADORA3) and about 15% for other targets which include Tyrosine-protein kinase JAK2, Adenosine A2a receptor, Phosphodiesterase 5A and Cathepsin K. The results of molecular docking showed that binding energy of cipargamin to PfATPase4 and hADORA3 are -12.40 kcal/mol and -13.40 kcal/mol respectively. This study has shown the possibility of malaria drug cipargamin modulating the activities of PfATP4 of the parasite (Plasmodium falciparum) as well as ADORA3 of the host (Homo sapiens). All the previous studies of cirpagamin have not implicated its action on hADORA3, thus this study provide insight to possible role of hADORA3 in the mechanism of malarial infection.