Is the ADP ribose site of the Chikungunya virus NSP3 Macro domain a target for antiviral approaches?
ACTA TROPICA
Authors: Shimizu, Jacqueline Farinha; Silva Martins, Daniel Oliveira; McPhillie, Martin J.; Roberts, Grace C.; Zothner, Carsten; Merits, Andres; Harris, Mark; Gomes Jardim, Ana Carolina
Abstract
Chikungunya virus (CHIKV) is a mosquito-transmitted virus of special concern as it causes Chikungunya fever, characterized by an acute febrile illness, rash, and arthralgia that can progress to chronic and debilitating arthritic symptoms. The effects of climate change on the geographic distribution of the mosquito vector has the potential to expose more of the globe to this virus. No antiviral agents or vaccines are currently available against CHIKV infection and the development of novel therapies that may lead to a future treatment is therefore necessary. In this context, the ADP-ribose binding site of the CHIKV nsP3 macro domain has been reported as a potential target for the development of antivirals. Mutations in the ADP-ribose binding site demonstrated decreased viral replication in cell culture and reduced virulence. In this study, 48,750 small molecules were screened in silico for their ability to bind to the ADP-ribose binding site of the CHIKV nsP3 macro domain. From this in silico analysis, 12 molecules were selected for in vitro analysis using a CHIKV subgenomic replicon in Huh-7 cells. Cell viability and CHIKV replication were evaluated and molecules C5 and C13 demonstrated 53 and 66% inhibition of CHIKV replication, respectively. By using a CHIKV-Dual luciferase replicon contain two reporter genes, we also demonstrated that the treatment with either compounds are probably interfering in the early replication rather than after RNA replication has occurred.
Converting formaldehyde-methylethylketone adduct to a nonlinear C5 1,3-diol over Pt-ceria catalysts for isoprene production
APPLIED CATALYSIS A-GENERAL
Authors: Qi, Yanlong; Liu, Shijun; Cui, Long; Dai, Quanquan; Bai, Chenxi
Abstract
Isoprene has outmost importance in the manufacture of elastomer. Herein, an alternative approach for isoprene production from readily available chemicals is reported: condensation of methyl ethyl ketone and formaldehyde, followed by the hydrogenation and dehydration reaction. The focus was paid on the hydrogenation reaction over Pt-ceria catalysts giving 2-methyl-1,3-butanediol, where the influence of Ce species on the catalyst structure was studied, and the structure-activity relationship was established. It deduced that the presence of CeO2 appeared to be essential for the catalyst structure (e.g., dispersion, morphology) and the enhanced catalytic performance (e.g., activating H-2, facilitating the reaction), these benefited from the presence of the oxygen vacancies on CeO2 surface. In addition, a relatively weak Pt-support interaction gave larger Pt particles which resulted in a higher yield. Finally, the application of the as-synthesized 2-methyl-1,3-butanediol in isoprene production was performed in the presence of the heteropolyacid catalysts, affording isoprene in similar to 80 % yield.