Ginger (Zingiber officinale) phytochemicals—gingerenone-A and shogaol inhibit SaHPPK: molecular docking, molecular dynamics simulations and in vitro approaches

Abstract

BackgroundAntibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Among several antibiotic resistant microbial consortium, Staphylococcus aureus is one of the most havoc microorganisms. Staphylococcus aureus encodes a unique enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), against which, none of existing antibiotics have been reported.MethodsComputational approaches have been instrumental in designing and discovering new drugs for several diseases. The present study highlights the impact of ginger phytochemicals on Staphylococcus aureus SaHPPK. Herein, we have retrieved eight ginger phytochemicals from published literature and investigated their inhibitory interactions with SaHPPK. To authenticate our work, the investigation proceeds considering the known antibiotics alongside the phytochemicals. Molecular docking was performed employing GOLD and CDOCKER. The compounds with the highest dock score from both the docking programmes were tested for their inhibitory capability in vitro. The binding conformations that were seated within the binding pocket showing strong interactions with the active sites residues rendered by highest dock score were forwarded towards the molecular dynamic (MD) simulation analysis.ResultsBased on molecular dock scores, molecular interaction with catalytic active residues and MD simulations studies, two ginger phytochemicals, gingerenone-A and shogaol have been proposed as candidate inhibitors against Staphylococcus aureus. They have demonstrated higher dock scores than the known antibiotics and have represented interactions with the key residues within the active site. Furthermore, these compounds have rendered considerable inhibitory activity when tested in vitro. Additionally, their superiority was corroborated by stable MD results conducted for 100 ns employing GROMACS package.ConclusionsFinally, we suggest that gingerenone-A and shogaol may either be potential SaHPPK inhibitors or can be used as fundamental platforms for novel SaHPPK inhibitor development.Electronic supplementary materialThe online version of this article (10.1186/s12941-018-0266-9) contains supplementary material, which is available to authorized users.

Computational search for potential COVID-19 drugs from FDA-approved drugs and small molecules of natural origin identifies several anti-virals and plant products

“…Virtual screening for the shallow site also predicted natural products with high medicinal value such as Gingerenone A (SN00156190) and Shogaol (SN00002189), but with lower docking score (table 1 ). Gingerenone A has anti-obesity, anti-inflammatory and antibiotic properties (Rampogu et al 2018 ; Suk et al 2017 ), whereas Shogaol is anticancer, anti-oxidant, antimicrobial, anti-inflammatory anti-allergic and antibiotic in nature (Rampogu et al 2018 ; Semwal et al 2015 ). MD simulation was not performed for the above two because of their lower rank but can be tested further.…”

“…Anticancer, anti-oxidant, antimicrobial, anti-inflammatory anti-allergic and antibiotic (Rampogu et al 2018;Semwal et al 2015) Molecules marked in bold have been discussed in the text.…”

An Unexplored Lewis Acidic Catalytic System for Synthesis of Pyrazole and its Biaryls Derivatives with Antimicrobial Activities through Cycloaddition‐Iodination‐Suzuki Reaction

“…Diverse conformations were obtained by adapting the random rigid body rotation. Ten conformers were allowed for each ligand while keeping all the other parameters as default …”

Recognition and interaction of CphA from Aeromonas hydrophila with imipenem and biapenem by spectroscopic analysis in combination with molecular docking

“…PyMOL and Discovery Studio 4.5 programs were acquired on analysis and drawing for the molecular docking . The binding free energy of the CphA‐antibiotic complex was calculated using the molecular force field method …”

“…19,20 The binding free energy of the CphA-antibiotic complex was calculated using the molecular force field method. [21][22][23] 3 | RESULTS AND DISCUSSION 3.1 | Expression and activity of CphA…”