Molecular Docking study of Catechins compounds from Camellia sinensis against UPPS in Staphylococcus aureus

Antibiotics resistant Staphylococcus aureus (S. aureus) is an emerging concern in the medical field. Due to their increasing resistance to numerous antibiotics, there is indeed essential to explore both potential targets and effective antibiotics. Therefore, we considered undecaprenyl diphosphate synthase (UPPS) as a potential target as it is an essential enzyme in cell wall biosynthesis of S. aureus. Earlier reports on these four major compounds from Camellia sinensis plant extract such as catechins (C), epicatechin (EC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) suggested that it could be an effective antibacterial agent. Thus, we attempt to validate the antibacterial activity of these compounds against UPPS via molecular docking analysis. Interestingly, we found that epicatechin gallate (ECg) has the highest binding energy with UPPS protein by forming nine hydrogen bonds with the amino acid residues at the binding site of the receptor. Hence, our results infer that ECg from Camellia sinensis poses significant anti-bacterial activities. Thus, the aim of this study was to provide an effective antibacterial molecule and potent target which might be helpful in further modification to increase their sensitivity

Datasets comprising the quality validations of simulated protein-ligand complexes and SYBYL docking scores of bioactive natural compounds as inhibitors of protein-targets.

Docking scores and simulation parameters to study the potency of natural compounds against protein targets in (M) were retrieved through molecular docking and structural investigation. The molecular docking datasets comprised 15 natural compounds, seven conventional anti-tuberculosis (anti-TB) drugs and their seven corresponding M target proteins. M protein targets were actively involved in translation mechanism, nucleic acid metabolism and membrane integrity. Standard structural screening and stereochemical optimizations were adopted to generate the 3D protein structures and their corresponding ligands prior to molecular docking. Force-field integration and energy minimization were further employed to obtain the proteins in their ideal geometry. Surflex-dock algorithm using Hammerhead scoring functions were used to finally produce the docking scores between each protein and the corresponding ligand(s). The best-docked complexes selected for simulation studies were subjected to topology adjustments, charge neutralizations, solvation and equilibrations (temperature, volume and pressure). The protein-ligand complexes and molecular dynamics parameter files have been provided. The trajectories of the simulated parameters such as density, pressure and temperature were generated with integrated tools of the simulation suite. The datasets can be useful to computational and molecular medicine researchers to find therapeutic leads relevant to the chemical behaviours of a specific class of compounds against biological systems. Structural parameters and energy functions provided a set of standard values that can be utilised to design simulation experiments regarding similar macromolecular interactions

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Vaccine repurposing approach for preventing COVID 19: can MMR vaccines reduce morbidity and mortality?

The coronavirus disease (COVID-19) is resulting in millions of infected individuals with several hundred thousands dead throughout the world. Amidst all the havoc, one interesting observation in the present COVID-19 pandemic is the negligible symptoms in the young; particularly children below 10 years of age. We assume the extensive pediatric vaccination with MMR vaccines followed globally could have resulted in innate immune responses, e.g., induction of interferons (IFNs) and activated natural killer (NK) cells, thereby offering natural immunity against SARS-CoV-2 in the young population. Possible cross-protective innate immunity offered by MMR vaccination prompted us to suggest repurposing MMR vaccination for immuno-prophylaxis against COVID-19

Multi-Epitope Vaccine for Monkeypox Using Pan-Genome and Reverse Vaccinology Approaches

Outbreaks of monkeypox virus infections have imposed major health concerns worldwide, with high morbidity threats to children and immunocompromised adults. Although repurposed drugs and vaccines are being used to curb the disease, the evolving traits of the virus, exhibiting considerable genetic dynamicity, challenge the limits of a targeted treatment. A pan-genome-based reverse vaccinology approach can provide fast and efficient solutions to resolve persistent inconveniences in experimental vaccine design during an outbreak-exigency. The approach encompassed screening of available monkeypox whole genomes (n = 910) to identify viral targets. From 102 screened viral targets, viral proteins L5L, A28, and L5 were finalized based on their location, solubility, and antigenicity. The potential T-cell and B-cell epitopes were extracted from the proteins using immunoinformatics tools and algorithms. Multiple vaccine constructs were designed by combining the epitopes. Based on immunological properties, chemical stability, and structural quality, a novel multi-epitopic vaccine construct, V4, was finalized. Flexible-docking and coarse-dynamics simulation portrayed that the V4 had high binding affinity towards human HLA-proteins (binding energy &lt; &minus;15.0 kcal/mol) with low conformational fluctuations (&lt;1 &Aring;). Thus, the vaccine construct (V4) may act as an efficient vaccine to induce immunity against monkeypox, which encourages experimental validation and similar approaches against emerging viral infections

R521C and R521H mutations in FUS result in weak binding with Karyopherinβ2 leading to Amyotrophic lateral sclerosis: a molecular docking and dynamics study

<p>Fused in sarcoma (FUS) gene encodes the RNA binding protein FUS. This gene is mapped to chromosome 16p11.2. The FUS protein binds with karyopherineβ2 (Kapβ2) through its proline/tyrosine nuclear localization signal (PY-NLS) that helps in the localization of FUS protein within the nucleus. Arginine residue in 521 position (R521) of PY-NLS plays a vital role in the binding of FUS protein with Kapβ2. Mutations in this position (R521C and R521H) are the most predominant mutations associated with amyotrophic lateral sclerosis (ALS). However, the mechanism by which these mutations lead to ALS is poorly understood. We examined the binding behaviour of the mutants FUS (R521C) and FUS (R521H) with Kapβ2 through protein–protein docking and molecular dynamics simulation. The binding patterns of mutants were compared with the binding behaviour of wild FUS–Kapβ2. Our results suggest that these mutants have relatively weak binding affinity with Kapβ2 when compared with wild FUS–Kapβ2 as indicated by the lesser number of interactions found between the mutant FUS and Kapβ2. Hence, these mutations weakens the binding and this results in the cytoplasmic mislocalization of mutant FUS; and thereby it increases the severity of ALS.</p

Detection of OXA-1 β-lactamase gene of Klebsiella pneumoniae from blood stream infections (BSI) by conventional PCR and in-silico analysis to understand the mechanism of OXA mediated resistance.

Klebsiella pneumoniae strains producing extended-spectrum β-lactamases (ESBL) exhibit resistance to antibiotic classes. The production of ESBLs (TEM-1, TEM-2, SHV-1, OXA-1) results in resistance to ampicillin, ticarcillin, piperacillin and cephalosporins. High levels of β-lactamases leads to development of resistance to β-lactamase inhibitors. The present study deals with characterizing antimicrobial resistance pattern among septicemia causing K. pneumoniae and the prevalence of inhibitor resistant OXA-1 β-lactamase genes among them. Of 151 study isolates, 59 were resistant to piperacillin/tazobactam and these isolates were further selected for blaOXA-1 screening. Amplification of β-lactamases genes by conventional PCR showed the presence of blaOXA-1 genes among 12 K. pneumoniae (20.3%) isolates. OXA-1 β-lactamase producing strains were found to be resistant to piperacillin/tazobactam(100%), levofloxacin (91.6%), amikacin (75%), cefoxitin (50%), ertapenem (25%), imipenem (16.6%) and meropenem (16.6%); all were susceptible to tigecycline. 3D models of OXA-1 β-lactamase were generated and docking was performed with various β-lactam antibiotics. Molecular docking (MD) revealed the molecular basis of drug sensitivity. MD simulation results clearly confirmed the notable loss in stability for tigecycline-blaOXA-1 complex. Findings of the present study will provide useful insights for understanding the mechanism of resistance and help with strategies for the development of new antibiotics. The conventional PCR assay designed in this study can be routinely used in clinical microbiology laboratories to determine the blaOXA-1 genes