The therapeutic activities of food-derived bioactive proteins and peptides are attracting increased attention within the research community. Medicinal plants used in traditional medicines are an excellent source of bioactive proteins and peptides, especially those traditionally prepared by water extraction for use as tea or food supplement. In this study, novel bioactive peptides were isolated from enzymatic digests of 33 Thai medicinal plants. The inhibitory activity of each against dengue virus (DENV) infection was investigated. Of 33 plants, peptides from Acacia catechu extract demonstrated the most pronounced anti-DENV activity. Half maximal inhibitory concentration of 0.18 μg/ml effectively inhibited DENV foci formation. Treatment with 1.25 μg/ml crude peptide extract could reduce virus production less than 100-fold with no observable cell toxicity. Peptide sequences were determined by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry. Two bioactive peptides isolated from Acacia catechu inhibited DENV foci formation >90% at the concentration of 50 μM; therefore, they are recommended for further investigation as antiviral peptides against DENV infection.

The enoyl-acyl carrier protein reductase InhA of M. tuberculosis is an attractive, validated target for anti-tuberculosis drug development. Moreover, direct inhibitors of InhA remain effective against InhA variants with mutations associated with isoniazid resistance, offering the potential for activity against MDR isolates. Here, structure based virtual screening supported by biological assays was applied to identify novel InhA inhibitors as potential antituberculosis agents. High-speed Glide SP docking was initially performed against two conformations of InhA differing in the orientation of the active site Tyr158. The resulting hits were filtered for drug-likeness based on Lipinski's rule and avoidance of PAINS-like properties, and finally subjected to Glide XP docking to improve accuracy. Sixteen compounds were identified and selected for in vitro biological assays, of which two (compounds 1 and 7) showed MIC of 12.5 and 25 µg/ml against M. tuberculosis H37Rv, respectively. Inhibition assays against purified recombinant InhA determined IC50 values for these compounds of 0.38 and 0.22 µM, respectively. A crystal structure of the most potent compound, compound 7, bound to InhA revealed the inhibitor to occupy a hydrophobic pocket implicated in binding the aliphatic portions of InhA substrates but distant from the NADH cofactor, i.e. in a site distinct from those occupied by the great majority of known InhA inhibitors. This compound provides an attractive starting template for ligand optimization aimed at discovery of new and effective compounds against M. tuberculosis that act by targeting InhA.

BackgroundEpidermal growth factor receptor (EGFR) signalling plays a major role in biological processes, including cell proliferation, differentiation and survival. Since the over-expression of EGFR causes human cancers, EGFR is an attractive drug target. A tumor suppressor endogenous protein, MIG-6, is known to suppress EGFR over-expression by binding to the C-lobe of EGFR kinase. Thus, this C-lobe of the EGFR kinase is a potential new target for EGFR kinase activity inhibition. In this study, molecular dynamics (MD) simulations and binding free energy calculations were used to investigate the protein-peptide interactions between EGFR kinase and a 27-residue peptide derived from MIG-6_s1 segment (residues 336–362).ResultsThese 27 residues of MIG-6_s1 were modeled from the published MIG-6 X-ray structure. The binding dynamics were detailed by applying the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method to predict the binding free energy. Both van der Waals interactions and non-polar solvation were favorable driving forces for binding process. Six residues of EGFR kinase and eight residues of MIG-6_s1 residues were shown to be responsible for interface binding in which we investigated per residue free energy decomposition and the results from the computational alanine scanning approach. These residues also had higher hydrogen bond occupancies than other residues at the binding interface. The results from the aforementioned calculations reasonably agreed with the previous experimental mutagenesis studies.ConclusionsMolecular dynamics simulations were used to investigate the interactions of MIG-6_s1 to EGFR kinase domain. Our study provides an insight into such interactions that is useful in guiding the design of novel anticancer therapeutics. The information on our modelled peptide interface with EGFR kinase could be a possible candidate for an EGFR dimerization inhibitor.

Yellow head virus (YHV) is one of the causative agents of shrimp viral disease. The prevention of YHV infection in shrimp has been developed by various methods, but it is still insufficient to protect the mass mortality in shrimp. New approaches for the antiviral drug development for viral infection have been focused on the inhibition of several potent viral enzymes, and thus the YHV protease is one of the interesting targets for developing antiviral drugs according to the pivotal roles of the enzyme in an early stage of viral propagation. In this study, a theoretical modeling of the YHV protease was constructed based on the folds of several known crystal structures of other viral proteases, and was subsequently used as a target for virtual screening-molecular docking against approximately 1364 NCI structurally diversity compounds. A complex between the protease and the hit compounds was investigated for intermolecular interactions by molecular dynamics simulations. Five best predicted compounds (NSC122819, NSC345647, NSC319990, NSC50650, and NSC5069) were tested against bacterial expressed YHV. The NSC122819 showed the best inhibitory characteristic among the candidates, while others showed more than 50 % of inhibition in the assay condition. These compounds could potentially be inhibitors for curing YHV infection.

Introduction: Bua Bok or Centella asiatica (CA) is an Asian vegetable with antiinflammatory benefits. Asiaticoside, asiatic acid, madecassoside and madecassic have been characterised as major active ingredients with a wide range of pharmacological advantages. In manufacturing processes, high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LCMS) are used to routinely determine the active compounds in raw materials.Objectives: This research aims to explore anti-inflammatory properties, characterise metabolites and observe the biochemical changes of the inflammatory induced macrophages after pretreatment with the potential extracted fractions.Methods: Bua Bok leaf extracts were prepared. Macrophages were pretreated with non-toxic fractions to determine the anti-inflammatory action. Tentative metabolites of effective fractions were identified by LC-MS. Synchrotron fourier-transform infrared (S-FTIR) microspectroscopy was utilised to observe the biochemical change of the lipopolysaccharide (LPS)-induced cells after pretreatment with potential fractions.Results: Fractions of ethyl acetate, 30% and 100% ethanol highly increased the nitrile scavenging and suppressed the function of phospholipase A 2 . Fractions of 70% and 100% ethanol strongly decreased nitric oxide production. The comparison of 39 chemical compounds was presented. The change of proteins was improved after pretreatment of macrophages with fraction 70% ethanol. Fraction of 100% ethanol revealed the lipid accumulation was lower than 70% ethanol and diclofenac. Conclusion:While the anti-inflammatory actions of 70% and 100% ethanol were similar. S-FTIR expressed they inhibited inflammatory response with the distinct features of biomolecules. The S-FTIR, LC-MS and biological assay confidently provided the efficient strategies to inform the advantage of herbal extract on cellular organisation instead of a single compound.