In March and April, 2009, an outbreak of H1N1 influenza in Mexico had led to hundreds of confirmed cases and the death toll had risen to 160. The worldwide spread of H1N1 has been attracting global attention and arising an overwhelming fear. So far, the vaccine and remedy has been in urgent need. In this study, a QSAR model and pharmacophore map of neuraminidase (NA) type 1 (N1) contained two hydrogen bond acceptor features, one hydrogen bond donor feature, and one positive ionizable feature. NCI database was employed in virtual screen by the N1 pharmacophore map features. After screening, compounds were obtained and then docked into haemagglutinin type 1 (H1) to find out the candidate drugs for dual target of both N1 and H1. The candidate, NCI0353858, selected via virtual screening and docking, might be functional to this worldwide disease; consequently, further clinical investigations and scientific application are urgently demanded. We realize the proposed ligand does not have much validity without conducting a study on the stability of the protein-ligand complex by MD simulations and binding free energy, and such a study is underway and will be reported later in this journal. Nevertheless, the present study is clear, consistent and could give a rational explanation for the binding mode of the best selected ligand.

Aim: To explore the potent inhibitor from one of the Traditional Chinese medicine (TCM), Epimedium sagittatum. Methods: We predicted the potent compound, eS03b, de novo evolution from the four Epimedium sagittatum components were verified by molecular docking, pharmacophore analysis, and analysis of quantitative structure-activity relationship (QSAR) model, which was constructed by multiple linear regression. Results: ES03b was chosen to undergo drug modification via de novo evolution. By analyzing the pharmacophore features, we found that the hydrophobic core in the binding site and the hydrogen bond generated at Asn663 played key roles in designing PDE5 inhibitors. eS03b generated 49 diversities (evo01-49). evo48 had high activity in prediction. Although the value of prediction was overestimated, evo48 was suggested as the potent lead. Conclusion: In this study, we showed that the hydrophobic core in the binding site and hydrogen bond production on Asn663 played key roles to design PDE5 inhibitors. From several require validation analysis, Evo48 was suggested to be a potent inhibitor.

In this study, we aimed at producing a MFNP consist of a dielectric core encapsulated fluorescein coating by a thin gold shell, which facilitate it with highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. We have composed a novel multi-functional nanodesign, Sample A3, with fluorescein encapsulated in SiO2 nanoparticles with gold shell. The A3 nanoparticles were uniform in size, no aggregation, homogeneous and stable in the solution under the SEM image system. We have also investigated its cytotoxicity to A10 human smooth muscle cell line by MTT assay, and found that the novel sample A3 were of little cytotoxic to the cells. In conclusion, we have proposed a novel method of preparing multi-functional nanoparticles assemblies, which has added fluorescein to SiO2 in a gold shell, to make it simultaneously have the functions of photothermal therapy and tracer.

AMP-activated protein kinase (AMPK) is a metabolite- sensed protein kinase in various eukaryotes. The activated AMPK regulates important proteins which cause diabetes, obesity, metabolic aberrant, and also breast cancer. In this study, the yeast AMPK structure was used as a template to model the human AMPK structure. By homology modeling, the reliable AMPK structure was built, and the active binding site was defined corresponding to X-ray crystal structure of yeast AMPK By virtual screening the database., All the potent ligands had the H-bond interaction in the key residues, same as the control. Thus, we suggested the phenylamide derivates might be the potent AMPK agonists.