Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides

Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry. We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein. By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity. The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay. The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively. These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery

Incorporating mindfulness: questioning capitalism

This paper engages with Buddhist critiques of capitalism and consumerism; and it challenges the capitalist appropriations of Buddhist techniques. We show how Buddhist modernism and Marxism/socialism can align, and how Engaged Buddhism spawns communalism and socially revolutionary impulses for sustainability and ecological responsibility within the framework of Buddhist thought and mindfulness traditions. Our case study of the Thai Asoke community exemplifies Buddhist communal mindfulness-in-action, explores successes and idiosyncrasies, and shows how communal principles can operate in such work-based communities

Lignocellulolytic capability of endophytic Phyllostica sp.

International audienceThe Dothideomycetes represent the largest fungal class of Ascomycota. It is an ubiquitous class of fungi whose members span a wide spectrum of lifestyles and host interactions. The endophytic fungus Phyllosticta is one members of the Dothideomycetes, causing disease in economic crops. Phyllosticta was screened for the degradation of lignocellulosic biomass of commercial relevance, such as rice straw, rice husk, sorghum, wheat straw, miscanthus, lavender flower, and lavender straw. The highest degrading strains were identified from an initial screen and further analyzed for the secretion of lignocellulosic enzymes during growth on the different biomasses. With Phyllosticta capitalensis (MFLUCC14-0233), maximum activity of arabinase (944.18 U/ml culture), cellulase (27.10 U/ml), xylanase (10.85 U/ml), pectinase (465.47 U/ml), and laccase (35.68 U/ml) activities could be detected in the secretome during growth on lavender flowers and lavender straw. Phyllosticta capitalensis is thus an interesting new strain for the production of lignocellulosic enzymes during growth on cheap agro-industrial biomass

Englerulaceae (Dothideomycetes)

Dai, Dong-Qin, Boonmee, Saranyaphat, Tian, Qing, Xiao, Yuan-Pin, Bhat, D. Jayarama, Chukeatirote, Ekachai, Alias, S. Aisyah, Zhao, Rui-Lin, Wang, Yong, Hyde, Kevin D. (2014): Englerulaceae (Dothideomycetes). Phytotaxa 176 (1): 139-155, DOI: 10.11646/phytotaxa.176.1.14, URL: http://dx.doi.org/10.11646/phytotaxa.176.1.1