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Abstract Aflatoxin B1 (AFB1), the natural polyketide produced by Aspergillus flavus, has a potent carcinogenic effect on humans as well as animals. In the present study, the antifungal and anti-aflatoxigenic B1 activity of chemically characterized Zingiber officinale essential oil (ZOEO) was investigated via in vitro analysis aided with molecular dynamics (MD) approaches. The GC–MS results revealed verbenol (52.41%) as the major component of oil. The antifungal and anti-aflatoxigenic activity of ZOEO was found to be 0.6 µl/ml and 0.5 µl/ml respectively. In-vitro analysis targeting the cell membrane, mitochondria and carbohydrate catabolism elucidated the probable antifungal mode of action. Further, docking and MD simulation results confirmed the inhibitory action of verbenol on the structural gene products (Nor-1, Omt-1, and Vbs) of aflatoxin biosynthetic machinery. Biochemical assays revealed the fungitoxic potential of the ZOEO while, computational results infers the stabilizing effects on the gene products upon verbenol binding leads to the impairment in its functionality. This is the first attempt to assess the multi-regime anti-AFB1 mechanism of verbenol chemotype-ZOEO targeting the Nor-1, Omt-1, and Vbs via computational approaches.

Tuberculosis (TB) is a recurrent and progressive disease, with high mortality rates worldwide. The drug-resistance phenomenon of Mycobacterium tuberculosis is a major obstruction of allelopathy treatment. An adverse side effect of allelopathic treatment is that it causes serious health complications. The search for suitable alternatives of conventional regimens is needed, i.e., by considering medicinal plant secondary metabolites to explore anti-TB drugs, targeting the action site of M. tuberculosis. Nowadays, plant-derived secondary metabolites are widely known for their beneficial uses, i.e., as antioxidants, antimicrobial agents, and in the treatment of a wide range of chronic human diseases (e.g., tuberculosis), and are known to “thwart” disease virulence. In this regard, in silico studies can reveal the inhibitory potential of plant-derived secondary metabolites against Mycobacterium at the very early stage of infection. Computational approaches based on different algorithms could play a significant role in screening plant metabolites against disease virulence of tuberculosis for drug designing.

It is known that crowded molecular environment affects the structure, thermodynamics, and dynamics of macromolecules. Most of the previous works on molecular crowding have majorly focused on the behavior of the macromolecule with less emphasis on the behavior of the crowder and water molecules. In the current study, we have precisely focused on the behavior of the crowder, (ethylene glycol (EG)), salt ions, and water in the presence of a DNA with the increase of the EG concentration. We have probed the behavior of water and crowder using molecular dynamics (MD) simulation and by calculating localized thermodynamic properties. Our results show an interesting competition between EG and water molecules to make hydrogen bonds (H-bond) with DNA. Although the total number of H-bonds involving DNA with both EG and water remains essentially same irrespective of the increase in EG concentration, there is a proportional change in the H-bonding pattern between water-water, EG-EG, and EG-water near DNA and in bulk. At low concentrations of EG, the displacement of water molecules near DNA is relatively easy. However, the displacement of water becomes more difficult as the concentration of EG increases. The density of Na+ (Cl-) near DNA increases (decreases) as the concentration of EG is increased. The density of Cl- near Na+ increases with the increase in EG concentration. It was also found that the average free energy per water in the first solvation shell increases with the increase in EG concentration. Putting all these together, a microscopic picture of EG, water, salt interaction in the presence of DNA, as a function of EG concentration, has emerged.