Phenoxybenzenes and phenoxypyridines were prepared and tested for the effect of substituents on antipicornavirus activity. The most active compound, 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (8), demonstrated broad-spectrum antipicornavirus activity. Compound 8 and several analogues each given orally prior to and during infection protected mice against an otherwise lethal challenge with coxsackievirus A21.
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A cardioviral 2C-ATP complex structure reveals the essential role of a conserved arginine in regulation of cardioviral 2C activity.
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Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
Unlabelled: 2C is a highly conserved picornaviral non-structural protein with ATPase activity and plays a multifunctional role in the viral life cycle as a promising target for anti-picornavirus drug development. While the structure-function of enteroviral 2Cs have been well studied, cardioviral 2Cs remain largely uncharacterized. Here, an endogenous ATP molecule was identified in the crystal structure of 2C from encephalomyocarditis virus (EMCV, Cardiovirus A).
View Article and Find Full Text PDFThe Upf1 protein restricts EV-A71 viral replication.
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Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial and Children's Hospital, Linkou 33305, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou 33305, Taiwan. Electronic address:
Enterovirus A71 (EV-A71) is transmitted through the respiratory tract, gastrointestinal system, and fecal-oral routes. The main symptoms caused by EV-A71 are hand, foot, and mouth disease (HFMD) or vesicular sore throat. Upf1 (Up-frameshift protein 1) was reported to degrade mRNA containing early stop codons, known as nonsense-mediated decay (NMD).
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Department of Pharmacognosy, College of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
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View Article and Find Full Text PDFIdentification of quinone analogues as potential inhibitors of picornavirus 3C protease in vitro.
Bioorg Med Chem Lett
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Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34114, Republic of Korea. Electronic address:
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- * Researchers conducted a high-throughput screening of approximately 6,000 small molecules to find potential inhibitors of the picornavirus 3C protease.
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Allosteric Regulation of Phosphatidylinositol 4-Kinase III Beta by an Antipicornavirus Compound MDL-860.
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August 2017
The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences , 26 Academician Georgi Bonchev Street, 1113 Sofia, Bulgaria.
MDL-860 is a broad-spectrum antipicornavirus compound discovered in 1982 and one of the few promising candidates effective in in vivo virus infection. Despite the effectiveness, the target and the mechanism of action of MDL-860 remain unknown. Here, we have characterized antipoliovirus activity of MDL-860 and identified host phosphatidylinositol-4 kinase III beta (PI4KB) as the target.
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