Novel Small Molecule Targeting the Hemagglutinin Stalk of Influenza Viruses.

Combating influenza is one of the perennial global public health issues to be managed. Antiviral drugs are useful for the treatment of influenza in the absence of an appropriate vaccine. However, the appearance of resistant strains necessitates a constant search for new drugs. In this study, we investigated novel anti-influenza drug candidates using in vitro and in vivo assays. We identified anti-influenza hit compounds using a high-throughput screening method with a green fluorescent protein-tagged recombinant influenza virus. Through subsequent analyses of their cytotoxicity and pharmacokinetic properties, one candidate (IY7640) was selected for further evaluation. In a replication kinetics analysis, IY7640 showed greater inhibitory effects during the early phase of viral infection than the viral neuraminidase inhibitor oseltamivir. In addition, we observed that hemagglutinin (HA)-mediated membrane fusion was inhibited by IY7640 treatment, indicating that the HA stalk region, which is highly conserved across various (sub)types of influenza viruses, may be the molecular target of IY7640. In an escape mutant analysis in cells, amino acid mutations were identified at the HA stalk region of the 2009 pandemic H1N1 (pH1N1) virus. Even though the in vivo efficacy of IY7640 did not reach complete protection in a lethal challenge study in mice, these results suggest that IY7640 has potential to be developed as a new type of anti-influenza drug.IMPORTANCE Anti-influenza drugs with broad-spectrum efficacy against antigenically diverse influenza viruses can be highly useful when no vaccines are available. To develop new anti-influenza drugs, we screened a number of small molecules and identified a strong candidate, IY7640. When added at the time of or after influenza virus infection, IY7640 was observed to successfully inhibit or reduce viral replication in cells. We subsequently discovered that IY7640 targets the stalk region of the influenza HA protein, which exhibits a relatively high degree of amino acid sequence conservation across various (sub)types of influenza viruses. Furthermore, IY7640 was observed to block HA-mediated membrane fusion of H1N1, H3N2, and influenza B viruses in cells. Although it appears less effective against strains other than H1N1 subtype viruses in a challenge study in mice, we suggest that the small molecule IY7640 has potential to be optimized as a new anti-influenza drug.

The photocatalytic destruction of cimetidine using microwave-assisted TiO2 photocatalysts hybrid system.

Microwave/Microwave discharge electrodeless lamp/Dissolved Oxygen/TiO2 photocatalyst hybrid system was applied to evaluate the photocatalytic degradation behavior of cimetidine, one of the waste drug components. The effects of microwave intensity, pH and dissolved oxygen (DO) concentration on the reaction rate of cimetidine (CMT) degradation were experimentally evaluated. In addition, the CMT decomposition reactions were compared by the combination of unit technologies of the hybrid system. As the microwave intensity and pH of the aqueous reactant solution increased, the CMT decomposition rate increased, and the DO concentration of the aqueous reactant solution had an optimum efficiency concentration. The highest CMT degradation efficiency was obtained by microwave/microwave discharge electrodeless lamp/TiO2 photocatalytic hybrid system at pH and DO concentration conditions (pH 10, DO 40 ppm). These results show that operation parameters and combination methods affect hydroxyl radical formation and CMT decomposition reactions on TiO2 surfaces, and efficient CMT decomposition reactions are formed through optimized hybrid systems. CMT is mineralized to CO2 and H2O through chemically active species (superoxide anion radical and hydroxyl radicals) via cimetine sulfoxide, 4-methyl-5-hydroxymethylimidazole, and sulfinyl-containing N-cyano-N',N'-dimethyl-guanidine.

Degradation behaviors of naproxen by a hybrid TiO2 photocatalyst system with process components.

A hybrid system combining microwave and a microwave discharge electrodeless lamp (MDEL) was proposed to overcome the limitations of conventional TiO2 photocatalysts. The degradation efficiency and mechanism of naproxen were determined using a series of single processes, including conventional TiO2 photocatalyst reactors and a hybrid system that fuses them. Although the degradation efficiency tended to increase after changing the experimental condition of a single process, the optimal conditions existed for these experimental conditions. On the other hand, remarkable synergy was observed in the fused process, whose efficiency was significantly higher than that of the unit process. In particular, the optimal degradation ability was obtained by adding hydrogen peroxide together with microwave irradiation. The seven intermediates in the proposed photocatalytic degradation pathway were generated by the demethylation and hydroxylation by hydroxyl radicals. These results are expected to provide new data on the design of high efficiency photocatalytic systems at low cost.

Heterogeneous photocatalytic degradation and hydrogen evolution from ethanolamine nuclear wastewater by a liquid phase plasma process.

Ethanolamine in a wastewater which is released from nuclear power plant was decomposed using a plasma discharged into the solution directly. Ni-TiO2 supported on mesoporous materials were employed as a photocatalyst. The photocatalytic reaction using the liquid phase plasma led to a degradation of ethanolamine with hydrogen evolution, simultaneously. The ethanolamine in the wastewater was degraded over 90% on the photocatalytic decomposition reaction by irradiation of liquid phase plasma. The rate of hydrogen evolution increased significantly with Ni incorporation on TiO2 because the bandgap was reduced with Ni incorporation on TiO2. Incorporating Ni on TiO2 nanocrystallites brought out an improvement of the ethanolamine degradation with hydrogen generation. The rate of hydrogen evolution in the ethanolamine-containing aqueous solution was increased in comparison with that in pure water. Additional hydrogen evolution by the photodecomposition of ethanolamine was attributed to the increasing H2 production.