In silico identification of organosulfur compounds from Allium ascalonicum L. as potential inhibitors of influenza A (H5N1): integrated DFT, docking, and molecular dynamics analysis

In Silico Evaluation of Betaine, DL-Stachydrine, and Choline from Shipworm (Spathoteredo obtusa) Extract as Antibacterial Agents Candidates Against Vibrio alginolyticus via LuxR Targeting

Bacterial infections caused by Vibrio alginolyticus represent a major challenge in aquaculture, leading tosignificant economic losses and increasing concerns regarding antibiotic resistance. This study aimed to evaluatethe potential of bioactive compounds from shipworm (Spathoteredo obtusa) as antibacterial and quorum sensinginhibitory agents through an in silico approach targeting the LuxR protein. Active compound screening using LC-HRMS identified three dominant compounds, namely betaine, DL-stachydrine, and choline. Molecular dockinganalysis was performed using PyRx, while ligand–protein interactions were visualized using Discovery Studio2021. The docking results showed that all tested compounds were able to interact with the LuxR protein withvarying binding affinity values. DL-stachydrine exhibited the best binding affinity among the tested compounds(-4.5 kcal/mol), followed by betaine (-3.9 kcal/mol) and choline (-3.8 kcal/mol), whereas the control quercetinshowed a substantially stronger binding affinity (-7.8 kcal/mol). Interaction analysis revealed the involvement ofhydrogen bonding, π-interactions, hydrophobic interactions, and van der Waals interactions within the LuxRbinding pocket. Several compounds also showed consistent interactions with key amino acid residues, suggestingbiologically relevant binding regions. These findings indicate that the tested compounds possess potential asantibacterial and quorum sensing inhibitory agents by targeting LuxR. However, further in vitro and in vivostudies are required to validate their biological activity and therapeutic potential.

In Silico Evaluation of Betaine, DL-Stachydrine, and Choline from Spathoteredo obtusa Extract as Potential LuxR Inhibitors Against Vibrio alginolyticus

In silico evaluation of novel metabolites from Tricholoma pardinum: Insights into drug-likeness, toxicity and target interactions via molecular docking and dynamics.

Six previously uncharacterized metabolites isolated from the poisonous mushroom Tricholoma pardinum are investigated using an integrated in silico approach to evaluate their therapeutic potential, highlighting the potential of metabolites from T. pardinum as novel scaffolds for developing anticancer agents targeting PARP1 and PIP4K2γ.

Design and in silico screening of novel isoniazid-based Schiff base derivatives followed by synthesis and biological evaluation of the lead compound against Mycobacterium tuberculosis H37Rv

The development of new antitubercular agents is critically needed due to the rising incidence of drug-resistant Mycobacterium tuberculosis. In the present study, a series of isoniazid-based Schiff base derivatives was designed and evaluated using an integrated in silico approach. A virtual library comprising 30 compounds was designed and systematically screened. Based on an integrated computational screening strategy involving drug-likeness evaluation, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling, Prediction of Activity Spectra for Substances (PASS) analysis, and molecular docking, the highest-ranked lead compound (SLB-5) was selected for synthesis, structural characterization, and biological evaluation. Molecular docking was performed against enoyl-acyl carrier protein reductase (InhA) of M. tuberculosis (PDB ID: 6EP8), identifying compounds with favorable predicted binding affinities ranging from − 8.7 to − 9.5 kcal/mol, which were more favorable than the docking score of isoniazid (− 5.8 kcal/mol). The selected lead compound, SLB-5, was synthesized via Schiff base condensation and characterized using Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H NMR), and high-resolution mass spectrometry (HRMS), confirming the formation of the azomethine (–C=N–) linkage. The antitubercular activity of SLB-5 was evaluated against M. tuberculosis H37Rv using the Alamar Blue assay, demonstrating concentration-dependent growth inhibition. Overall, the findings suggest that isoniazid-based Schiff base derivatives represent a promising scaffold for the development of new antitubercular agents. The study demonstrates the utility of an integrated computational screening workflow for prioritizing lead compounds for synthesis and biological evaluation, with SLB-5 emerging as a promising candidate for further investigation.

Identification of Potential Compounds of Green Tea (Camellia sinensis) in Inhibiting SARS-CoV-2: a Multi-Target Approach Based on Molecular Docking

SARS-CoV-2 is a new betacoronavirus that has a complex replication pathway through the Mpro, TMPRSS2, and RdRp proteins. This study aims to analyze the potential and molecular mechanisms of catechin-derived compounds from green tea (Camellia sinensis), using a multi-target approach based on molecular docking. Predictions of physicochemical properties and toxicity were analyzed using SwissADME, pkCSM, and Toxtree v3.1.0.1851. Protein and ligand structure preparation used PDB, MolView, and Avogadro. Then, molecular docking was analyzed using AutoDock4 1.5.6 and BIOVIA Discovery Studio. The analysis results showed that the EGCG compound had the best affinity with Mpro (-7.6 kcal/mol) at the cyad catalytic site (His 41 and Cys 145), the CG compound with TMPRSS2 (-7.95 kcal/mol) at the triad catalytic site (His 26 and Ser 441), and the ECG compound with RdRp (-7.51 kcal/mol) at the replication catalytic site (Lys 73 and Phe 219). These results indicate that the catechin compound from green tea has the potential to inhibit SARS-CoV-2 replication in a multi-target manner through the mechanism of inhibition of the catalytic and replication sites, thereby overcoming the complexity of virus replication and avoiding resistance

Computational Discovery of Phytochemicals Targeting InhA of Mycobacterium tuberculosis: Insights from Molecular Docking, MMGBSA, ADME Profiling, and Molecular Dynamics Simulations.

INTRODUCTION Tuberculosis (TB) is one of the most serious global health issues, with the increasing number of multidrug-resistant TB cases emphasizing the need for new therapeutic approaches. Phytochemicals, with their diverse structures and favorable safety profiles, are a largely unexplored area for anti-TB drug development. METHODS An ethnobotanical study and literature analysis identified 310 medicinal plants traditionally used to treat respiratory infections, which produced 4,087 phytochemicals. Their structures were obtained from PubChem or drawn using ChemDraw, and pharmacokinetic properties were analyzed using QikProp. Enoyl-acyl carrier protein reductase (InhA, PDB ID: 4TRO), an important enzyme involved in mycolic acid biosynthesis, was selected as the target protein. Molecular docking was performed using Glide, followed by MMGBSA calculations, and the best hits were validated by 300 ns molecular dynamics simulations using the GROMACS pipeline. RESULTS Binding affinities showed that four phytochemicals, namely Patuletin, skimmin, flavonol- 3-O-D-glycoside, and salicin, had significantly higher binding affinity scores (-10.06 to -8.82 kcal/mol) than first-line anti-TB drugs isoniazid (-6.35 kcal/mol) and pyrazinamide (-4.22 kcal/mol). Patuletin and skimmin had MM-GBSA binding affinity scores of -74.89 and -71.76 kcal/mol, respectively. MD simulations of the top 3 compounds and control showed that the protein-ligand complexes were stable, as indicated by the RMSD, RMSF, Radius of gyration, SASA, and HBONDS. DISCUSSION Patuletin and Skimmin demonstrated strong binding affinity and structural stability against the InhA enzyme (PDB: 4TRO), indicating their potential as promising lead compounds for anti-tuberculosis effects. Derived from ethnomedicinal plants, these phytochemicals not only target key mycobacterial pathways but may also offer hepatoprotective and immunomodulatory benefits. The findings support the exploration of plant-derived compounds as safer and effective alternatives or adjuncts to conventional anti-TB therapies. CONCLUSION The combination of virtual screening, ADME studies, and MD simulations enabled the identification of phytochemicals with promising interactions toward InhA, an established anti-TB target. The findings are based solely on computational analysis and should be interpreted as preliminary evidence of target engagement rather than confirmed inhibitory activity or therapeutic efficacy. These natural products may serve as potential lead compounds for further anti-tubercular drug discovery, warranting subsequent biochemical, cellular, and in vivo validation to establish their inhibitory potential, safety, and pharmacological effectiveness.