Highly pathogenic influenza viruses have become a global threat to humans. It is important to select an effective therapeutic option suitable for the subtypes in an epidemic or pandemic. To increase the options, the development of novel antiviral agents acting on targets different from those of the currently approved drugs is required. In this study, we performed molecular dynamics simulations on a spike protein on the viral envelop, hemagglutinin, for the wild-type and three kinds of mutants using a model system consisting of a trimeric hemagglutinin complex, viral lipid membrane, solvation waters, and ions. A natural product, stachyflin, which shows a high level of antiviral activity specific to some subtypes of influenza viruses, was examined on binding to the wild-type hemagglutinin by docking simulation. The compound potency of stachyflin is, however, easily lost due to resistant mutations. From a comparison of simulation results between the wild-type and the resistant mutants, the reason for the drug resistance of hemagglutinin was clarified. Next, 8 compounds were selected from a chemical database by in silico screening, considering the findings from the simulations. Inhibitory activities to suppress the proliferation of influenza virus were measured by cell-based antiviral assays, and two chemical scaffolds were found to be potent for an inhibitor. More than 30 derivatives bearing either of these two chemical scaffolds were synthesized, and cell culture assays were carried out to evaluate the compound potency. Several derivatives displayed a high compound potency, and 50% effective concentrations of two synthesized compounds were below 1 μM.
Chirally arranged organic dye-linked polysilsesquioxane was prepared, through a sol–gel transcription using its non-chiral precursor with a chiral supramolecular template, and its chiroptical properties were investigated.
We demonstrate that lanthanide ions doped in nanometrical silica helices with chirally arranged siloxane network without any organic mediates show induced chiroptical properties such as circular dichroism and circularly polarized...
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