Virtual screening of flavonoids against Plasmodium vivax Duffy binding protein utilizing molecular docking and molecular dynamic simulation

Plasmodium vivax ( P. vivax ) is one of the highly prevalent human malaria parasites. Due to the presence of extravascular reservoirs and recurrent infections from latent liver stages, P. vivax is extremely challenging to manage and eradicate. Traditionally, herbs have been widely used to combat various diseases. Flavonoids from plants are investigated against viral and infectious diseases and showed some promising results to combat these disorders. In the present study, in silico approaches are utilized to study the effect of flavonoids against P. vivax to inhibit malarial invasion of human red blood cells (RBC). Duffy binding protein (DBP) is a malarial protein responsible for binding the Duffy antigen receptor for chemokines (DARC) on human red blood cells and causes malarial invasion. The main focus is to block the DBP binding site to restrict the formation of the DBP-DARC complex. A molecular docking study was performed to analyze the interaction of flavonoid molecules with the DARC-binding site of DBP of P. vivax . Furthermore, molecular dynamic simulation studies are carried out to study the stability of top-docked complexes. The results showed the good effectiveness of flavonoids such as daidzein, genistein, kaempferol, and quercetin in the DBP binding site. These flavonoids bind with DBP and blocked its active site. Furthermore, the binding of these four ligands was maintained throughout the 50 ns simulation maintaining stable hydrogen bond formation with the active site residues of DBP. The present study suggests that flavonoids might be good candidates and novel agents against DBP-mediated RBC invasion of P. vivax .