Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N/L26I and M2-S31N/V27A from the influenza A viruses.
In this study, we identified four amantadine-resistant M2 mutants among avian and human influenza A H5N1 strains circulating between 2002 to 2019: the single S31N and V27A mutants, and the S31N/L26I and S31N/V27A double mutants. Herein, utilizing two-electrode voltage clamp (TEVC) assays, we screened a panel of structurally diverse M2 inhibitors against these single and double mutant channels. Three compounds 6, 7, and 15 were found to significantly block all three M2 mutants: M2-S31N, M2-S31N/L26I, and M2-S31N/V27A. Using recombinant viruses generated from reverse genetics, we further showed that these compounds also inhi...
Source: European Journal of Pharmaceutical Sciences - October 25, 2019 Category: Drugs & Pharmacology Authors: Musharrafieh R, Ma C, Wang J Tags: Eur J Pharm Sci Source Type: research
Amantadine resistance markers among low pathogenic avian influenza H9N2 viruses isolated from poultry in India, during 2009–2017
In conclusion, the present study reports prevalence and gradual increase of amantadine resistance among AI H9N2 viruses in India, emphasizing the importance of the antiviral surveillance. (Source: Microbial Pathogenesis)
Source: Microbial Pathogenesis - October 8, 2019 Category: Infectious Diseases Source Type: research
Enhancing Hepatitis C Virus pseudoparticles infectivity through p7NS2 cellular expression.
In conclusion, we report the establishment of a stable production system of HCVpp with enhanced infectivity through the overexpression of p7NS2 ORF contributing to improve HCV entry assessment assays widely used in antiviral drug discovery and vaccine development.
PMID: 31412271 [PubMed - as supplied by publisher] (Source: Journal of Virological Methods)
Source: Journal of Virological Methods - August 10, 2019 Category: Virology Authors: Soares HR, Ferreira-Fernandes M, Marchel M, Alves PM, Coroadinha AS Tags: J Virol Methods Source Type: research
Molecules, Vol. 24, Pages 1828: Optical Resolution of Rimantadine
A. Soloshonok
This work discloses a new procedure for the resolution of commercially available racemic rimantadine hydrochloride to enantiomerically pure (S)-rimantadine using (R)-phenoxypropionic acid as a recyclable resolving reagent. Good chemical yields, operational ease, and low-cost structure underscore the preparative value of this method for the production of enantiomerically pure rimantadine for medicinal or synthetic studies. (Source: Molecules)
Source: Molecules - May 11, 2019 Category: Chemistry Authors: Jianlin Han Ryosuke Takeda Tatsunori Sato Hiroki Moriwaki Hidenori Abe Kunisuke Izawa Vadim A. Soloshonok Tags: Article Source Type: research
Rapid Evolution and Gene Communication of H3N2 and H1N1 Influenza A Viruses
Recently, it is reported in Journal of infection that H5N61 and H7N92 subtype avian influenza virus may have an increased pathogenicity to humans.The H1N1 subtype influenza virus has emerged in China. Not only the H1N1 (95%) subtype but also several H3N2 (5%) subtype influenza viruses have been detected in samples. According to Chinese national influenza data (http://ivdc.chinacdc.cn/ ) , the H1N1 subtype influenza virus was prevalent from the end of 2018 to the beginning of 2019. The H1N1 and H3N2 subtypes of influenza virus are resistant to adamantanes (amantadine and rimantadine), and a small number of H1N1 strains have...
Source: Journal of Infection - March 21, 2019 Category: Infectious Diseases Authors: Xiao Li, jianglin Chen, Jingkai Hu, Xuanjiang Jin, Shumin Xie, Zhixian Li, Xiao Wang, Yixue Dai, Ming Liao, Weixin Jia Tags: Letter to the Editor Source Type: research
Computational Study of HCV p7 Channel: Insight into a New Strategy for HCV Inhibitor Design
AbstractHCV p7 protein is a cation-selective ion channel, playing an essential role during the life cycle of HCV viruses. To understand the cation-selective mechanism, we constructed a hexameric model in lipid bilayers of HCV p7 protein for HCB JFH-1 strain, genotype 2a. In this structural model, His9 and Val6 were key factors for the HCV cation-selective ion channel. The histidine residues at position 9 in the hexameric model formed a first gate for HCV p7 channel, acting as a selectivity filter for cations. The valines mentioned above formed a second gate for HCV p7 channel, serving as a hydrophobic filter for the dehydr...
Source: Interdisciplinary Sciences, Computational Life Sciences - September 7, 2018 Category: Bioinformatics Source Type: research
Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5
Publication date: Available online 7 August 2018Source: Antiviral ResearchAuthor(s): Laura F. Wetherill, Christopher W. Wasson, Gemma Swinscoe, David Kealy, Richard Foster, Stephen Griffin, Andrew MacdonaldAbstractDespite the availability of prophylactic vaccines the burden of human papillomavirus (HPV) associated malignancy remains high and there is a need to develop additional therapeutic strategies to complement vaccination. We have previously shown that the poorly characterised E5 oncoprotein forms a virus-coded ion channel or viroporin that was sensitive to the amantadine derivative rimantadine. We now demonstrate tha...
Source: Antiviral Therapy - August 8, 2018 Category: Virology Source Type: research
Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5.
Abstract
Despite the availability of prophylactic vaccines the burden of human papillomavirus (HPV) associated malignancy remains high and there is a need to develop additional therapeutic strategies to complement vaccination. We have previously shown that the poorly characterised E5 oncoprotein forms a virus-coded ion channel or viroporin that was sensitive to the amantadine derivative rimantadine. We now demonstrate that alkylated imino sugars, which have antiviral activity against a number of viruses, inhibit E5 channel activity in vitro. Using molecular modelling we predict that imino sugars intercalat...
Source: Antiviral Research - August 7, 2018 Category: Virology Authors: Wetherill LF, Wasson CW, Swinscoe G, Kealy D, Foster R, Griffin S, Macdonald A Tags: Antiviral Res Source Type: research
Magnetic-assisted biotinylated single-chain variable fragment antibody-based immunoassay for amantadine detection in chicken.
Abstract
A sensitive competitive immunoassay with simple operation was developed for the detection of the anti-virus drug amantadine (AMD). The single-chain variable fragment (scFv) antibody against AMD was site-specific biotinylated and overexpressed as a secreted body in Escherichia coli AVB101. Horseradish peroxidase-labeled streptavidin-biotinylated scFv antibody (HRP-SA-BIO-scFv) could specifically bind to AMD-functionalized magnetic beads (MBs) and then the immune complexes were separated from the matrix solution by magnet. The concentration of the AMD could be known by the measurement of the signal ...
Source: Analytical and Bioanalytical Chemistry - July 14, 2018 Category: Chemistry Authors: Xie S, Wen K, Xie J, Zheng Y, Peng T, Wang J, Yao K, Ding S, Jiang H Tags: Anal Bioanal Chem Source Type: research
Second-order asymmetric transformation and its application for the practical synthesis of α-amino acids
Org. Biomol. Chem., 2018, Advance Article DOI: 10.1039/C8OB00963E, CommunicationRyosuke Takeda, Akie Kawamura, Aki Kawashima, Tatsunori Sato, Hiroki Moriwaki, Kunisuke Izawa, Hidenori Abe, Vadim A. Soloshonok Design of a rimantadine [1-(1-adamantyl)ethanamine]-derived chiral ligand and its application for the preparation of α-amino acidsvia second-order asymmetric transformation is reported. To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic and Biomolecular Chemistry)
Source: RSC - Organic and Biomolecular Chemistry - July 10, 2018 Category: Molecular Biology Authors: Ryosuke Takeda Source Type: research
Second-order asymmetric transformation and its application for the practical synthesis of [small alpha]-amino acids
Org. Biomol. Chem., 2018, Advance Article DOI: 10.1039/C8OB00963E, CommunicationRyosuke Takeda, Akie Kawamura, Aki Kawashima, Tatsunori Sato, Hiroki Moriwaki, Kunisuke Izawa, Hidenori Abe, Vadim A. Soloshonok Design of a rimantadine [1-(1-adamantyl)ethanamine]-derived chiral ligand and its application for the preparation of [small alpha]-amino acidsvia second-order asymmetric transformation is reported. To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic and Biomolecular Chemistry)
Source: RSC - Organic and Biomolecular Chemistry - June 27, 2018 Category: Molecular Biology Authors: Ryosuke Takeda Source Type: research
Second-order asymmetric transformation; Application for practical synthesis of [small alpha]-amino acids
We report a discovery of new rimantadine [1-(1-adamantyl)ethanamine]-derived chiral ligand and its application for preparation of [small alpha]-amino acids using second-order asymmetric transformation apporach. The operational ease of experimental procedures coupled... The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic and Biomolecular Chemistry)
Source: RSC - Organic and Biomolecular Chemistry - June 19, 2018 Category: Molecular Biology Authors: Ryosuke Takeda Source Type: research
Simultaneous determination of amantadine and rimantadine in feed by liquid chromatography-Qtrap mass spectrometry with information-dependent acquisition.
Abstract
A sensitive method for simultaneous determination of amantadine and rimantadine in feed was developed using an ultra-high-performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry (UHPLC-Qtrap-MS) in the multiple reaction monitoring information-dependent acquisition-enhanced product ion (MRM-IDA-EPI) mode, and employing the mixed cation exchange (MCX) solid-phase extraction column as sample cleanup and amantadine-d15 and rimantadine-d4 as internal standards, respectively. Compared to traditional MRM mode, for the targeted drugs in feed simultaneously both the secondary ...
Source: Analytical and Bioanalytical Chemistry - April 13, 2018 Category: Chemistry Authors: Jia Q, Li D, Wang X, Yang S, Qian Y, Qiu J Tags: Anal Bioanal Chem Source Type: research
Unraveling the Binding, Proton Blockage, and Inhibition
of Influenza M2 WT and S31N by Rimantadine Variants
ACS Medicinal Chemistry LettersDOI: 10.1021/acsmedchemlett.7b00458 (Source: ACS Medicinal Chemistry Letters)
Source: ACS Medicinal Chemistry Letters - February 14, 2018 Category: Chemistry Authors: Antonios Drakopoulos, Christina Tzitzoglaki, Kelly McGuire, Anja Hoffmann, Athina Konstantinidi, Dimitrios Kolokouris, Chunlong Ma, Kathrin Freudenberger, Johanna Hutterer, Gu ̈nter Gauglitz, Jun Wang, Michaela Schmidtke, David D. Busath and Antonios Kol Source Type: research
