Computational insights into the inhibitory potential of cyclotides Psyle B and Psyle C against key surface proteins of avian influenza H5N1.

In silico docking and molecular dynamics simulation analysis of phytochemicals targeting human metapneumovirus fusion protein

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

Influenza A (H5N1) remains a major public health concern due to its high pathogenicity and ongoing viral evolution, underscoring the need for novel antiviral candidates. In this study, we performed an integrated in silico evaluation of organosulfur compounds derived from Allium ascalonicum L. (shallot) cultivated in the Tolaki-Mekongga region, Sulawesi, Indonesia, targeting key viral proteins including polymerase (PB2), nucleoprotein (NP), and neuraminidase (NA). Density functional theory (DFT) analyses were conducted to characterize the electronic properties of the compounds, while PASS prediction indicated moderate potential antiviral activity for Propanethiol and Dipropyl disulfide. Pharmacokinetic profiling suggested acceptable ADMET properties for several candidates. Molecular docking revealed favorable binding conformations across all targets, with γ-glutamyl-S-propenylcysteine exhibiting the most favorable binding energies among the evaluated organosulfur compounds (PB2: -4.9 kcal/mol; NP: -5.8 kcal/mol; NA: -5.2 kcal/mol). These values were comparable to those of oseltamivir and favipiravir for NP and NA, although weaker binding was observed against PB2. Subsequent simulations of molecular dynamics demonstrated stable protein–ligand complexes over 100 ns, further supporting the predicted binding interactions. Consistently, MM-GBSA calculations indicated favorable binding free energies, particularly for γ-glutamyl-S-propenylcysteine (PB2: -30.52 ± 0.29 kcal/mol; NP: -22.76 ± 0.12 kcal/mol; NA: -26.13 ± 0.35 kcal/mol). Overall, these findings suggest that shallot-derived organosulfur compounds, especially γ-glutamyl-S-propenylcysteine, exhibit potential for interaction with H5N1 viral targets and may warrant further investigation as antiviral candidates. Experimental validation through in vitro and in vivo studies is required to confirm their biological activity and therapeutic potential.

IN SILICO EVALUATION OF ANTIVIRAL POTENTIAL OF EMBLICA OFFICINALIS PHYTOCONSTITUENTS TARGETING CHIKUNGUNYA VIRUS NSP3 PROTEIN

Findings suggest that bioactive compounds from E. officinalis may serve as promising candidates for the development of anti-CHIKV therapeutics, however, further experimental validation is required to confirm their efficacy and safety.

Virtual Screening of Bacteriocins From Lactic Acid Bacteria Against Monkeypox DNA Polymerase: Sakacin P and Mundticin KS Emerge as Promising Candidates

ABSTRACT The monkeypox virus (MPXV) has recently risen to be a significant global health threat and currently there are no approved antiviral agents, which makes it necessary to develop new antiviral strategies. In this study, we employed in silico techniques to investigate whether bacteriocins could be potent inhibitors of the MPXV DNA polymerase (MPDP). At first, the MPXV DNA polymerase enzyme chain was extracted from the Cryo‐EM structure of MPXV DNA replication complex and was then assessed using SWISS‐MODEL/QMEAN for structural quality. The structures of selected bacteriocins were either retrieved from the Protein Data Bank or predicted using AlphaFold. The quality of these predicted models was measured by LGscore. Moreover, the physicochemical properties of the selected bacteriocins, such as Sakacin P and Mundticin KS, were analyzed to assess their molecular stability and compatibility with the molecular docking process. The results of protein‐peptide docking simulations on the HADDOCK platform showed that among all the bacteriocins tested, Sakacin P and Mundticin KS had the highest binding affinities toward MPXV DNA polymerase. The analysis of the docking experiments also revealed vital stabilizing interactions, such as the formation of hydrogen bonds, ionic linkages, and π–π stacking, which were crucial in the strength of the protein–ligand complexes. Subsequently, the molecular dynamics (MD) simulations further confirmed the stability of the protein–bacteriocin complexes. Our results indicate that bacteriocins, especially Sakacin P and Mundticin KS, can be considered potential antiviral agents against MPXV by interfering with its DNA replication mechanism. The present work shall serve as a reference for future laboratory testing and for the promising innovation of bacteriocin‐based drugs targeting MPXV.

Dual Mechanisms of Apigenin and Luteolin Against Dengue Virus Serotype 2: Allosteric Inhibition of NS2B/NS3 Protease and Interference with Host C-Type Lectin Receptor-Mediated Entry

Objective: This study aimed to perform a computational analysis of apigenin and luteolin, focusing on their biological activities, pharmacokinetic properties, and interactions with dengue virus serotype 2 (DENV-2) proteins and host cell receptors associated with viral entry.Material and Methods: The biological activities of the compounds were first predicted using PASS Online to evaluate their potential pharmacological profiles. Pharmacokinetic properties, including gastrointestinal absorption, skin permeation, blood–brain barrier penetration, cytochrome P450 interactions, bioavailability score, and overall drug-likeness, were assessed using SwissADME. In addition, toxicity parameters, such as LD₅₀ values and organ-specific toxicities, were predicted using ProTox 3.0. Subsequently, molecular docking simulations were performed using the SeamDock web server to evaluate the binding affinities of the compounds with dengue viral proteins and host receptor targets.Results: Both compounds exhibited favorable pharmacokinetic characteristics and low predicted toxicity, alongside antioxidant and anti-inflammatory activities. Docking simulations revealed that luteolin had a slightly stronger affinity (−7.74 kcal/mol) than apigenin (−7.67 kcal/mol) toward the NS2B-NS3 protease, particularly at allosteric sites. In addition, both flavonoids displayed interactions with host C-type lectin receptors, suggesting potential interference with viral attachment and entry mechanisms.Conclusion: These computational findings highlight apigenin and luteolin as promising anti-dengue candidates with dual mechanisms of action through viral protease inhibition and host receptor interactions, supported by favorable pharmacokinetic and safety profiles.

An In Silico and In Vitro Approach to Identify Potential Phytocompounds as Inhibitors of Pneumolysin, a Secretory Toxin of Streptococcus pneumoniae

Pneumolysin (PLY), a cholesterol-dependent cytolysin produced by Streptococcus pneumoniae, plays a key role in the pathogenesis of bacterial pneumonia. The present study aimed to identify potential phytocompound inhibitors of pneumolysin and evaluate their protective effects against toxin-induced cytotoxicity using combined in silico and in vitro approaches. A ligand library comprising 200 phytocompounds was constructed using three-dimensional structures obtained from the PubChem database, while the PLY protein structure was retrieved from the Protein Data Bank. Molecular docking was performed to analyse protein-ligand interactions, followed by visualization using BIOVIA Discovery Studio Visualizer. Top-ranked phytocompounds from docking were further screened by computational ADME analysis, followed by molecular dynamics (MD) simulations for stability analysis. Selected compounds were then validated using RAW 264.7 macrophages, and cytotoxicity was assessed by flow cytometry. Among the screened compounds, three showed high binding affinity, with oridonin exhibiting the most favourable interaction profile (−7.906 kcal/mol). MD simulation confirmed the stability of the pneumolysin–oridonin complex. In vitro results demonstrated that pneumolysin induced significant, concentration-dependent cytotoxicity, whereas pre-incubation with oridonin significantly reduced cell death. To provide direct functional evidence of pneumolysin inhibition, haemolysis inhibition assay using sheep erythrocytes was performed where reduction of pneumolysin-mediated haemolysis by oridonin in a concentration-dependent manner was demonstrated. These findings suggest that oridonin may serve as a potential inhibitor of pneumolysin-mediated cytotoxicity and pneumococcal virulence.