A COMPUTATIONAL APPROACH ON UNDERSTANDING STRUCTURAL INTERACTIONS OF ENVELOPE PROTEIN OF DENGUE VIRUS BOUND WITH SQUALENE, A PROTOTYPE ANTI-VIRAL COMPOUND

Objective: The objective of the work was to validate the structural binding affinity of Squalene with the envelope protein of Dengue virus by means of molecular simulations. Methods: Three-dimensional (3D) structure of dengue 2 virus envelope protein was retrieved from Protein Data Bank PDB and Squalene compound from the ZINC database. Molecular docking between the E protein and Squalene were carried out by means of Auto Dock 4.2. Results: Based on the study, it was observed that the binding/docking energy for the complex structure was calculated to be-5.55 kcal/mol. Critical residues to interact with E protein were scrutinized by analyzing the interface of the complex within 4 Å proximity. Residues such as Thr 48, Glu49, Ala 50, Val 130, Leu 135, Ser 186, Pro 187, Thr 189, Gly 190, Leu 191, Phe 193, Leu 198, Leu 207, Thr 268, Phe 279, Thr 280, Gly 281, His 282 and Leu 283 were found to be non-covalently located around the squalene. Conclusion: Scopes to design de novo anti-viral compounds to the dengue viruses by using squalene as a new class of template structure have also been concisely brought into fore

Facile synthesis of silver nanoparticles using Euphorbia antiquorum L. latex extract and evaluation of their biomedical perspectives as anticancer agents

This study reveals the rapid biosynthesis of silver nanoparticles (EAAgNPs) using aqueous latex extract of Euphorbia antiquorum L as a potential bioreductant. Synthesized EAAgNPs generate the surface plasmonic resonance peak at 438 nm in UVâVis spectrophotometer. Size and shape of EAAgNPs were further characterized through transmission electron microscope (TEM) which shows well-dispersed spherical nanoparticles with size ranging from 10 to 50 nm. Energy dispersive X-ray spectroscopic analysis (EDAX) confirms the presence of silver (Ag) as the major constituent element. X-ray diffraction (XRD) pattern of EAAgNPs corresponding to (111), (200), (220) and (311) planes, reveals that the generated nanoparticles were face centered cubic crystalline in nature. Interestingly, fourier-transform infrared spectroscopy (FTIR) analysis shows the major role of active phenolic constituents in reduction and stabilization of EAAgNPs. Phyto-fabricated EAAgNPs exhibits significant antimicrobial and larvicidal activity against bacterial human pathogens as well as disease transmitting blood sucking parasites such as Culex quinquefasciatus and Aedes aegypti (IIIrd instar larvae). On the other hand, in vitro cytotoxicity assessment of bioformulated EAAgNPs has shown potential anticancer activity against human cervical carcinoma cells (HeLa). The preliminary biochemical (MTT assay) and microscopic studies depict that the synthesized EAAgNPs at minimal dosage (IC50 = 28 μg) triggers cellular toxicity response. Hence, the EAAgNPs can be considered as an environmentally benign and non-toxic nanobiomaterial for biomedical applications. Keywords: Crystal structure, Euphorbia antiquorum L., Silver nanoparticles, Anticancer, Human pathogen

Response of three cyprinid fish species to the Scavenger Deterrent Factor produced by the mutualistic bacteria associated with entomopathogenic nematodes

Pachiappan, Perumal/0000-0002-6496-1607WOS: 000395227900006PubMed: 27908637The symbiotic bacteria, Photorhabdus and Xenorhabdus associated with entomopathogenic nematodes (EPNs) in the genera Heterorhabditis and Steinernema, respectively, produce a compound(s) called the Scavenging Deterrent Factor (SDF). SDF deters a number of terrestrial insect scavengers and predators and one bird species from feeding on host insects killed by the nematode-bacterium complex but has not been tested against aquatic vertebrates. Moreover, the Heterorhabditis-Photorhabdus association is believed to have evolved in an aquatic environment. Accordingly, we hypothesized that SDF will deter fish from feeding on nematode-killed insects and tested the responses of three omnivorous fresh water fish species, Devario aequipinnatus, Alburnoides bipunctatus, and Squalius pursakensis, to SDF in the laboratory. When the fish were exposed to Galleria mellonella larvae killed by the Heterorhabditis- or Steinernema-bacterium complex at 2 or 4 days post-infection, all three fish species made several attempts to consume the cadavers but subsequently rejected them. However, all fish species consumed freeze killed control larvae. In a choice test, when D. aequipinnatus or A. bipunctatus were offered a pair of nematode-killed larvae, both fish species rejected these cadavers; when offered a nematode-killed larva and a freeze-killed larva, both fish species consumed the freeze-killed larva but not the nematode-killed one. In further tests with D. aequipinnatus, there was no significant difference in the number of 2-day-old Bacillus thuringiensis subsp. kurstaki-killed (Btk) larvae consumed compared to freeze-killed larvae, but significantly fewer 4-day-old Btk-killed larvae were consumed compared to freeze-killed larvae. When D. aequipinnatus was fed G. mellonella larvae killed by the symbiotic bacteria, the fish rejected the cadavers. When given freeze-killed or nematode-killed mosquito (Aedes aegypti) larvae, the fish consumed significantly more of the former larvae (99%) compared to the latter (55%). When D. aequipinnatus was placed in a symbiotic cell-free supernatant for 18 h, a significant reduction in consumption of freeze killed larvae compared to cell-free Btk or control broth supernatant was observed. We showed that SDF protects the nematode-killed insects from being consumed by omnivorous fishes and suggests that they will have minimal effects on recycling of EPNs in the aquatic environment. (C) 2016 Elsevier Inc. All rights reserved.Government of India [SERB-DST-SB/YS/LS-176/2013]The senior author, R. Karthik Raja, is grateful to Government of India for providing financial support for this study (SERB-DST-SB/YS/LS-176/2013). We thank Drs. P. Indira Arulselvi and Reyaz Ahmad Lone, Periyar University, India for providing the Bacillus thuringiensis cultures, and Drs. David Shapiro-Ilan and Clive Bock, USDA, Byron, Georgia, USA for their review and comments on the draft manuscript

<i>Xenorhabdus stockiae</i> KT835471-mediated feasible biosynthesis of metal nanoparticles for their antibacterial and cytotoxic activities

<p>In this study, extracellular metabolites of symbiotic bacteria <i>Xenorhabdus stockiae</i> (KT835471) was employed for the synthesis of silver (XsAgNPs) and gold nanoparticles (XsAuNPs). Synthesized NPs were characterized using high throughput instrumentation which confirms the generation of stable, crystalline XsAgNPs and XsAuNPs with the mean size of 14 ± 6 and 14 ± 5, respectively. Further, the NPs exhibits an excellent bactericidal effect against six different pathogens. On the other hand, NPs displayed an outstanding anticancer activity against human lung adenocarcinoma epithelial cells (A549). Therefore, the present study strongly suggests that metal NPs encrusted with functional bio-moieties can be used for different biomedical applications.</p