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[Objective] Plasmodium vivax predominantly infects many people in numerous tropical areas, including Southeast Asia, the Western Pacific, the Americas, and the Eastern Mediterranean. The uniqueness of forming dormant stages can lead to relapse in vivax malaria upon further infection. This study used molecular docking and dynamic simulation to predict potential bioactive compounds from the Zingiberaceae plant family as inhibitors by targeting Plasmodium vivax Duffy Binding Protein (PvDBP). PvDBP-DARC molecular interaction is required to mediate the merozoite invasion process into red blood cells. Inhibiting this process can possibly control parasite growth and development. [Methodology] Molecular docking screening was conducted by using 138 natural compounds from the Zingiberaceae plant family targeting Plasmodium vivax Duffy binding protein (PvDBP). The top two compounds with the lowest binding energy were selected to be analyzed by pharmacokinetics prediction and molecular dynamic (MD) simulation. [Results] Molecular docking screening resulted in the top two compounds with the lowest binding energy value, including 5,7-dihydroxyflavanone (-9.3 kcal/mol) and pinostrobin (-9.2 kcal/mol). These compounds are predicted to have stronger interaction than chloroquine as a control. Furthermore, the potential compounds also interact with DARC binding site residues and maintain them during the molecular dynamic simulation process. Otherwise, chloroquine as a control cannot retain 75% binding residues towards PvDBP. A molecular dynamic study revealed that all three complexes have relatively similar stability. [Conclusions] We predicted that the two bioactive compounds (5,7-dihydroxyflavanone and pinostrobin) have the potential as merozoite invasion inhibitors.

Abstract The oncoprotein E6, a pivotal player in HPV-16-induced cancer, has long been the focus of extensive research. Building upon our previous study, we identified asarinin and thiazolo[3,2-a] benzimidazole-3(2H)-one-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo) as potential potent anti-HPV-16 E6 oncoprotein agents. Utilizing the UniProt-derived E6 sequence, we employed I-TASSER to model the protein's three-dimensional structure. Subsequent molecular docking via AutoDock Vina, coupled with a 1,000 ps dynamic analysis under physiological parameters, revealed that both asarinin and thiazolo have a high chance of forming stable protein-ligand complexes with HPV-16 E6, displaying distinct molecular dynamic properties. Thiazolo exhibited superior stability in simulation, evident in ligand conformation and movement graphs, while asarinin excelled in terms of contact residues. Furthermore, SASA, hydrogen bond graphs, and the DCCM graph collectively underscore the comparable potential of both drugs as robust inhibitors of the HPV-16 E6 oncoprotein.