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Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase.
Biochem J
July 2021
Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
The COVID-19 pandemic has presented itself as one of the most critical public health challenges of the century, with SARS-CoV-2 being the third member of the Coronaviridae family to cause a fatal disease in humans. There is currently only one antiviral compound, remdesivir, that can be used for the treatment of COVID-19. To identify additional potential therapeutics, we investigated the enzymatic proteins encoded in the SARS-CoV-2 genome.
View Article and Find Full Text PDFRe-evaluation of in vivo selectivity of [(11)C]SA4503 to σ(1) receptors in the brain: contributions of emopamil binding protein.
Nucl Med Biol
October 2012
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Naka, Itabashi, Tokyo 173-0022, Japan.
Introduction: Carbon-11-labeled 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine ([(11)C]SA4503) was shown to be a promising PET ligand for mapping σ(1) receptors, and was applied to human subjects. However, an in vitro study indicated that SA4503 also binds to the emopamil binding protein (EBP), vertebral Δ8-Δ7 sterol isomerase. To our knowledge, no information is available about the possibility of [(11)C]SA4503 binding to EBP in the brain in vivo.
View Article and Find Full Text PDFFlupentixol and trifluperidol reduce interleukin-1 beta and interleukin-2 release by rat mixed glial and microglial cell cultures.
Pol J Pharmacol
July 2005
Department of Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
Neuroleptics penetrate into the brain, where they act not only on neurons but probably also on glial cells. In the available literature, there are no reports on the effect of neuroleptics on cytokine release in glia cultures. The aim of this study was to evaluate the effect of neuroleptics on the release of proinflammatory cytokines (IL-1beta and IL-2) by mixed glial and microglial cell cultures.
View Article and Find Full Text PDFFlupentixol and trifluperidol reduce secretion of tumor necrosis factor-alpha and nitric oxide by rat microglial cells.
Neurochem Int
July 2003
Department of Clinical Pharmacology, Medical University of Silesia, 40-752 Katowice, 18, Medyków, Poland.
Tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), both of which are produced by activated microglial cells, are involved in the neuropathogenesis of many diseases affecting the central nervous system (CNS). There is a need to develop drugs that inhibit neurotoxic processes in neurodegenerative diseases. The aim of this study was to evaluate the effect of two neuroleptics, flupentixol and trifluperidol, on the release of pro-apoptotic TNF-alpha and NO by LPS-activated rat microglial cells.
View Article and Find Full Text PDF[The action of neuroleptics on different types of catalepsy in rats with a genetic predisposition to catatonic reactions].
Zh Vyssh Nerv Deiat Im I P Pavlova
August 1995
Rats of GC strain with genetic predisposition to cataleptic reactions bred from Wistar rats are more sensitive to cataleptogenic effect of haloperidol and trifluperidol than Wistar rats. At the same time, chlorpromazine and sulpiride considerably shorten the time of maintenance of imposed vertical cataleptic postures for which GC strain has been selected. This paradoxical situation is interpreted so that the more pronounced neuroleptic-induced catalepsy in GC rats is caused by increased sensitivity of postsynaptic dopamine D receptors in the striatum, while the predisposition to the cataleptic postures attenuated by neuroleptics is associated with dopaminergic hyperactivity of the mesolimbic system.
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