Inhibition of erectile dysfunction-related enzymes by ginger ( <i>Zingiber officinale</i> )-derived compounds: molecular docking and dynamics studies

Erectile dysfunction (ED) is one of the common forms of sexual disorder that significantly impacts the psychosocial quality of life amongst male folks. Previous studies have evidenced the role of arginase-1 (Arg-1), angiotensin-I-converting enzyme (ACE), phosphodiesterase-5 (PDE-5) and acetylcholinesterase (AChE) in the progression of this pathology. In the current investigation, a library of compounds present in <i>Zingiber officinale</i> was screened to discover lead therapeutic agents for potential inhibitors of these metabolic enzymes. The compounds were subjected to molecular docking analysis with the various proteins' standard inhibitors. Subsequently, the thermodynamic stability of the protein-ligand complexes of two top-docked compounds with the highest binding affinities for each protein was studied further <i>via</i> molecular dynamics (MD) using the CHARMM-GUI website. Moreover, the Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) pharmacological properties and drug-likeness of the top-docked 5 compounds from the plant were investigated with the SuperPred and the SwissADME web servers. From the compounds' library, diacetoxy-6-gingerdiol, 10-gingerdione, alloaromadendrene, valencene, and 6-gingerdiol showed the strongest inhibitory capacities with the amino acids present at the catalytic pocket of the selected proteins. Nonetheless, valencene and alloaromadendrene displayed better stability with the various protein complexes. Given that all these compounds were predicted to be non-toxic and have acceptable drug-likeness profiles, this investigation revealed their potential as a source of lead phytochemicals from regularly consumed food substances to mitigate the pathophysiology of erectile dysfunction. However, additional lab-based experiments are required before these phytochemicals can be developed into clinically approved commercially available drugs.