Heat capacity and decomposition of rimantadine hydrochloride
Publication date: Available online 30 January 2020Source: Thermochimica ActaAuthor(s): Ala Bazyleva, Eugene Paulechka, Dzmitry H. Zaitsau, Andrey V. Blokhin, Gennady J. KaboAbstractHeat capacities of the antiviral drug rimantadine hydrochloride in the crystalline state were measured by adiabatic calorimetry and differential scanning calorimetry in the temperature range from (7 to 453) K. A broad low-enthalpy solid-state phase anomaly was detected between (170 and 250) K. Thermodynamic functions for crystalline rimantadine hydrochloride were derived. Decomposition of the studied compound was probed by the Knudsen effusion m...
Source: Thermochimica Acta - February 1, 2020 Category: Chemistry Source Type: research

N-Isopropylsulfinylimines vs. N-tert-butylsulfinylimines in the stereoselective synthesis of sterically hindered amines: an improved synthesis of enantiopure (R)- and (S)-rimantadine and the trifluoromethylated analogues
Org. Biomol. Chem., 2019, Advance Article DOI: 10.1039/C9OB02241D, CommunicationNazaret Moreno, Roc ío Recio, Victoria Valdivia, Noureddine Khiar, Inmaculada Fernández In contrast toN-tert-butylsulfinylimines, the use ofN-isopropylsulfinylimines as starting chiral material allows the stereoselective synthesis of both enantiomers of rimantadine and its trifluoromethylated analogues. 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 - November 13, 2019 Category: Molecular Biology Authors: Nazaret Moreno Source Type: research

N-Isopropylsulfinylimines vs N-tert-butylsulfinylimines in the stereoselective synthesis of sterically hindered amines: An improved synthesis of enantiopure (R)- and (S)-rimantadine and the trifluoromethylated analogues.
Org. Biomol. Chem., 2019, Accepted Manuscript DOI: 10.1039/C9OB02241D, CommunicationNazaret Moreno, Rocio Recio, Victoria Valdivia, Noureddine Khiar, Inmaculada Fern ández Fernández An improved fully stereoselective synthesis of both enantiomers of rimantadine and its trifluoromethylated analogues has been developed, using N-isopropylsulfinylimines as starting chiral material, proving the superiority of the isopropyl group... The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic and Biomolecular Chemistry)
Source: RSC - Organic and Biomolecular Chemistry - November 4, 2019 Category: Molecular Biology Authors: Nazaret Moreno Source Type: research

Molecules, Vol. 24, Pages 3975: Automated Stopped-Flow Fluorimetric Sensor for Biologically Active Adamantane Derivatives Based on Zone Fluidics
haris A zone-fluidics (ZF) based automated fluorimetric sensor for the determination of pharmaceutically active adamantine derivatives, i.e., amantadine (AMA), memantine (MEM) and rimantadine (RIM) is reported. Discrete zones of the analytes and reagents (o-phthalaldehyde and N-acetylcysteine) mix and react under stopped-flow conditions to yield fluorescent iso-indole derivatives (λex/ λem = 340/455 nm). The proposed ZF sensor was developed and validated to prove suitable for quality control tests (assay and content uniformity) of commercially available formulations purchased from the Gree...
Source: Molecules - November 3, 2019 Category: Chemistry Authors: Paraskevas D. Tzanavaras Sofia Papadimitriou Constantinos K. Zacharis Tags: Article Source Type: research

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 26, 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 11, 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 12, 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 22, 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 intercalate betwee...
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 produced...
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 mass spe...
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

Understanding the inhibitory mechanism of BIT225 drug against p7 viroporin using computational study.
Abstract P7 is the only viral channel encoded by the Hepatitis C Virus (HCV) genome. It is a small, highly hydrophobic protein containing 63 amino acids. Structural studies have shown that p7 has two transmembrane (TM) α helices linked by a short dibasic cytoplasmic loop. P7, mostly placed in the endoplasmic reticulum (ER), is a membrane-associated protein. The results obtained from different studies revealed that p7 is a polytopic membrane protein that could oligomerize in membrane bilayer to create ion channels with cation selectivity. In addition, p7 is highly conserved and plays an important role in the ...
Source: Biophysical Chemistry - November 16, 2017 Category: Chemistry Authors: Behmard E, Abdolmaleki P, Taghdir M Tags: Biophys Chem Source Type: research

[Comment] Finding the right combination antiviral therapy for influenza
Influenza results in annual epidemics and global pandemics of acute respiratory illness that increases morbidity, mortality, and hospital admissions. Fortunately, there are currently two classes of antivirals licensed for the treatment of influenza in much of the world: the M2 inhibitiors (amantadine and rimantadine) and the neuraminidase inhibitors (oseltamivir, peramivir and zanamivir). There are also other antivirals licensed in Asia (laninamivir and favipiravir) and Russia (umifenovir). Additionally, a wide range of novel antivirals have been or are being studied in the treatment of influenza. (Source: The Lancet Infectious Diseases)
Source: The Lancet Infectious Diseases - September 22, 2017 Category: Infectious Diseases Authors: Michael G Ison Tags: Comment Source Type: research

Anti-influenza activity of diazaadamantanes combined with monoterpene moieties.
Abstract The antiviral activity of several diaza-adamantanes containing monoterpenoid moieties against a rimantadine-resistant strain of the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. Hetero-adamantanes containing monoterpene moieties at the aminal position of the heterocycle were found to exhibit lower activity compared to compounds with a diaza-adamantane fragment and a monoterpene moiety linked via an amino group at the 6-position of the hetero-adamantane ring. The highest selectivity index (a ratio of the 50% cytotoxic concentration to the 50% inhibitory concentration) out of 30 was observed for co...
Source: Bioorganic and Medicinal Chemistry Letters - September 1, 2017 Category: Chemistry Authors: Suslov E, Zarubaev VV, Slita AV, Ponomarev K, Korchagina D, Ayine-Tora DM, Reynisson J, Volcho K, Salakhutdinov N Tags: Bioorg Med Chem Lett Source Type: research

Stereoselective Synthesis of Novel Adamantane Derivatives with High Potency Against Rimantadine-Resistant Influenza A Virus Strains
Org. Biomol. Chem., 2017, Accepted Manuscript DOI: 10.1039/C7OB00331E, CommunicationNikolai Kuznetsov, Rabdan Tikhov, Ivan Godovikov, Michael Medvedev, Konstantin Lyssenko, Elena Burtseva, Elena Kirillova, Yurii N. Bubnov A series of (R)- and (S)-isomers of new adamantane-substituted heterocycles (1,3-oxazinan-2-one, piperidine-2,4-dione, piperidine-2-one and piperidine) with potent activity against rimantadine-resistant strains of Influenza A virus were synthesized through the transformation... The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic and Biomolecular Chemistry)
Source: RSC - Organic and Biomolecular Chemistry - March 10, 2017 Category: Molecular Biology Authors: Nikolai Kuznetsov Source Type: research

Influenza A Virus Nucleoprotein: A Highly Conserved Multi-Functional Viral Protein As A Hot Antiviral Drug Target.
Abstract Prevention and treatment of influenza virus infection is an ongoing unmet medical need. Each year, thousands of deaths and millions of hospitalizations are attributed to influenza virus infection, which poses a tremendous health and economic burden to the society. Aside from the annual influenza season, influenza viruses also lead to occasional influenza pandemics as a result of emerging or re-emerging influenza strains. Influenza viruses are RNA viruses that exist in quasispecies, meaning that they have a very diverse genetic background. Such a feature creates a grand challenge in devising therapeutic in...
Source: Current Topics in Medicinal Chemistry - February 24, 2017 Category: Chemistry Authors: Hu Y, Sneyd H, Dekant R, Wang J Tags: Curr Top Med Chem Source Type: research

Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited
ACS Medicinal Chemistry LettersDOI: 10.1021/acsmedchemlett.6b00311 (Source: ACS Medicinal Chemistry Letters)
Source: ACS Medicinal Chemistry Letters - January 27, 2017 Category: Chemistry Authors: Antonios Drakopoulos, Christina Tzitzoglaki, Chulong Ma, Kathrin Freudenberger, Anja Hoffmann, Yanmei Hu, Gu ̈nter Gauglitz, Michaela Schmidtke, Jun Wang and Antonios Kolocouris Source Type: research

An M2-V27A channel blocker demonstrates potent in  vitro and in vivo antiviral activities against amantadine-sensitive and -resistant influenza A viruses
Publication date: April 2017 Source:Antiviral Research, Volume 140 Author(s): Yanmei Hu, Rami Musharrafieh, Chunlong Ma, Jiantao Zhang, Donald F. Smee, William F. DeGrado, Jun Wang Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V27A mutant...
Source: Antiviral Therapy - January 20, 2017 Category: Virology Source Type: research

An M2-V27A channel blocker demonstrates potent in vitro and in vivo antiviral activities against amantadine-sensitive and -resistant influenza A viruses
Publication date: Available online 10 January 2017 Source:Antiviral Research Author(s): Yanmei Hu, Rami Musharrafieh, Chunlong Ma, Jiantao Zhang, Donald F. Smee, William F. DeGrado, Jun Wang Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V...
Source: Antiviral Therapy - January 11, 2017 Category: Virology Source Type: research

An M2-V27A channel blocker demonstrates potent in vitro and in vivo antiviral activities against amantadine-sensitive and -resistant influenza A viruses.
Abstract Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V27A mutant was found to be the predominant mutant under drug selection pressure, thereby representing a high profile antiviral drug target. Guided by molecular dynamics simul...
Source: Antiviral Research - January 10, 2017 Category: Virology Authors: Hu Y, Musharrafieh R, Ma C, Zhang J, Smee DF, DeGrado WF, Wang J Tags: Antiviral Res Source Type: research

Antiviral Treatments
Most viral respiratory tract infections are caused by classic respiratory viruses, including influenza, respiratory syncytial virus, human metapneumovirus, parainfluenza, rhinovirus, and adenovirus, whereas other viruses, such as herpes simplex, cytomegalovirus, and measles virus, can opportunistically affect the respiratory tract. The M2 inhibitors, amantadine and rimantadine, were historically effective for the prevention and treatment of influenza A but all circulating strains are currently resistant to these drugs. Neuraminidase inhibitors are the sole approved class of antivirals to treat influenza. Ribavirin, especia...
Source: Clinics in Chest Medicine - December 13, 2016 Category: Respiratory Medicine Authors: Michael G. Ison Source Type: research

Preparation of a monoclonal antibody against amantadine and rimantadine and development of an indirect competitive enzyme-linked immunosorbent assay for detecting the same in chicken muscle and liver
Publication date: 30 January 2017 Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 133 Author(s): Dapeng Peng, Wei Wei, Yuanhu Pan, Yulian Wang, Dongmei Chen, Zhenli Liu, Xu Wang, Menghong Dai, Zonghui Yuan A monoclonal antibody (mAb) was produced in order to monitor the illegal use of amantadine and rimantadine in animals. The produced mAb 2G3 exhibited an IC50 value of 15.8μgL−1 for amantadine and exhibited cross-reactivity to both amantadine (100%) and rimantadine (70.6%). Standard curves ranged from 5 to 80μgL−1 for 2G3. The limits of detection of the developed indirect competitive en...
Source: Journal of Pharmaceutical and Biomedical Analysis - November 24, 2016 Category: Drugs & Pharmacology Source Type: research

Anti-Influenza Virus Effects of Catechins: A Molecular and Clinical Review.
Abstract Influenza infection and associated epidemics represent a serious public health problem. Several preventive and curative measures exist against its spread including vaccination and therapeutic agents such as neuraminidase inhibitors (e.g., oseltamivir, zanamivir, as well as peramivir and laninamivir, which are licensed in several countries) and adamantanes (e.g., amantadine and rimantadine). However, neuraminidase inhibitor- and adamantane-resistant viruses have been detected, whereas vaccines exhibit strain-specific effects and are limited in supply. Thus, new approaches are needed to prevent and treat in...
Source: Current Medicinal Chemistry - November 22, 2016 Category: Chemistry Authors: Ide K, Kawasaki Y, Kawakami K, Yamada H Tags: Curr Med Chem Source Type: research

Involvement of a proton ‐coupled organic cation antiporter in the blood–brain barrier transport of amantadine
Abstract The blood‐to‐brain transport of amantadine, a weak N‐methyl‐d‐aspartate (NMDA) antagonist, has been shown previously to participate in the cationic drug‐sensitive transport system across the mouse blood–brain barrier (BBB). The purpose of the present study was to characterize the influx transport system by means of both an in situ mouse brain perfusion technique and in vitro studies using rat immortalized brain capillary endothelial cells (GPNT). The observed concentration‐dependent initial uptake rate of [3H]amantadine suggested the involvement of a carrier‐mediated transport mechanism. The ...
Source: Biopharmaceutics and Drug Disposition - August 24, 2016 Category: Drugs & Pharmacology Authors: Toyofumi Suzuki, Takahiko Aoyama, Naoto Suzuki, Masaru Kobayashi, Toshiro Fukami, Yoshiaki Matsumoto, Kazuo Tomono Tags: Original Paper Source Type: research

Patch-Clamp Study of Hepatitis C p7 Channels Reveals Genotype-Specific Sensitivity to Inhibitors.
Abstract Hepatitis C is a major worldwide disease and health hazard, affecting ∼3% of the world population. The p7 protein of hepatitis C virus (HCV) is an intracellular ion channel and pH regulator that is involved in the viral replication cycle. It is targeted by various classical ion channel blockers. Here, we generated p7 constructs corresponding to HCV genotypes 1a, 2a, 3a, and 4a for recombinant expression in HEK293 cells, and studied p7 channels using patch-clamp recording techniques. The pH50 values for recombinant p7 channels were between 6.0 and 6.5, as expected for proton-activated channels, and cur...
Source: Biophysical Journal - June 7, 2016 Category: Physics Authors: Breitinger U, Farag NS, Ali NK, Breitinger HG Tags: Biophys J Source Type: research

Adamantane - a lead structure for drugs in clinical practice.
Abstract he adamantane moiety is the structural backbone of numerous compounds and its discovery launched a new field of chemistry studying the approaches to the synthesis as well as the physicochemical and biological properties of organic polyhedral compounds with practical application in the pharmaceutical industry. Adamantane derivatives have proven to be very potent compounds in a wide range of applications from systemic to topical63 therapy. This review summarizes the currently available adamantane derivatives in clinical practice (amantadine, memantine, rimantadine, tromantadine, adapalene, saxagliptin, vild...
Source: Current Medicinal Chemistry - May 25, 2016 Category: Chemistry Authors: Spilovska K, Zemek F, Korabecny J, Nepovimova E, Windisch OS, Kuca K Tags: Curr Med Chem Source Type: research

Involvement of a Proton ‐Coupled Organic Cation Antiporter in the Blood‐Brain Barrier Transport of Amantadine
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - May 4, 2016 Category: Drugs & Pharmacology Authors: Toyofumi Suzuki, Takahiko Aoyama, Naoto Suzuki, Masaru Kobayashi, Toshiro Fukami, Yoshiaki Matsumoto, Kazuo Tomono Tags: Original Paper Source Type: research

Involvement of a Proton‐Coupled Organic Cation Antiporter in the Blood‐Brain Barrier Transport of Amantadine
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - April 1, 2016 Category: Drugs & Pharmacology Authors: Toyofumi Suzuki, Takahiko Aoyama, Naoto Suzuki, Masaru Kobayashi, Toshiro Fukami, Yoshiaki Matsumoto, Kazuo Tomono Tags: Original Paper Source Type: research

Intrathecal rimantadine induces motor, proprioceptive, and nociceptive blockades in rats
Publication date: 8 April 2016 Source:Neuroscience Letters, Volume 618 Author(s): Jann-Inn Tzeng, Jieh-Neng Wang, Jhi-Joung Wang, Yu-Wen Chen, Ching-Hsia Hung The purpose of the experiment was to evaluate the local anesthetic effect of rimantadine in spinal anesthesia. Rimantadine in a dose-dependent fashion was constructed after intrathecally injecting the rats with four different doses. The potency and duration of rimantadine were compared with that of the local anesthetic lidocaine at producing spinal motor, nociceptive, and proprioceptive blockades. We demonstrated that intrathecal rimantadine dose-dependently p...
Source: Neuroscience Letters - March 10, 2016 Category: Neuroscience Source Type: research

Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity.
Abstract Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus ra...
Source: Virology - March 4, 2016 Category: Virology Authors: Zhirnov OP, Manykin AA, Rossman JS, Klenk HD Tags: Virology Source Type: research

Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses
Publication date: May 2016 Source:Antiviral Research, Volume 129 Author(s): Jennifer L. McKimm-Breschkin, Alicia M. Fry The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2–4 June, 2015. With emerging resistance to the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme focus...
Source: Antiviral Therapy - February 23, 2016 Category: Virology Source Type: research

Meeting report: 4th ISIRVAntiviral Group Conference: Novel Antiviral Therapies for Influenza and Other Respiratory Viruses
Publication date: Available online 9 February 2016 Source:Antiviral Research Author(s): Jennifer L. McKimm-Breschkin, Alicia Fry The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2-4 June, 2015. With emerging resistance to the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme fo...
Source: Antiviral Therapy - February 10, 2016 Category: Virology Source Type: research

Meeting report: 4(th) ISIRVAntiviral Group Conference: Novel Antiviral Therapies for Influenza and Other Respiratory Viruses.
Abstract The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4(th) Antiviral Group Conference at the University of Texas on 2-4 June, 2015. With emerging resistance to the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme focused on the discovery and development of inhibitors of several virus targets and key host cell factors involved ...
Source: Antiviral Research - February 9, 2016 Category: Virology Authors: McKimm-Breschkin JL, Fry A Tags: Antiviral Res Source Type: research

Differential Binding of Rimantadine Enantiomers to Influenza A M2 Proton Channel
Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b13129 (Source: Journal of the American Chemical Society)
Source: Journal of the American Chemical Society - January 28, 2016 Category: Chemistry Authors: Anna K. Wright, Paratchata Batsomboon, Jian Dai, Ivan Hung, Huan-Xiang Zhou, Gregory B. Dudley and Timothy A. Cross Source Type: research

Amantadine resistance among highly pathogenic avian influenza viruses (H5N1) isolated from India
Publication date: Available online 27 November 2015 Source:Microbial Pathogenesis Author(s): Aron Jacob, Richa Sood, Kh.Victoria Chanu, Sandeep Bhatia, Rekha Khandia, A.K. Pateriya, S. Nagarajan, U. Dimri, D.D. Kulkarni Emergence of antiviral resistance among H5N1 avian influenza viruses is the major challenge in the control of pandemic influenza. Matrix 2 (M2) inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir) are the two classes of antiviral agents that are specifically active against influenza viruses and are used for both treatment and prophylaxis of influenza in...
Source: Microbial Pathogenesis - November 27, 2015 Category: Infectious Diseases Source Type: research

Influenza Antiviral Expenditures and Outpatient Prescriptions in the United States, 2003–2012
ConclusionInfluenza antivirals totaled $3.74 billion in the United States from 2003 to 2012, with the majority in 2009 and from community pharmacies. Influenza antivirals constituted a small proportion of total medication expenditures, but unforeseen pandemics resulted in unusually high use and expenditures. Influenza antiviral prescriptions dispensed from community pharmacies were associated with ILI and drug expenditures. (Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy)
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - November 23, 2015 Category: Drugs & Pharmacology Authors: Katie J. Suda, Robert J. Hunkler, Linda M. Matusiak, Glen T. Schumock Tags: Original Research Article Source Type: research

Investigation of the free energy profiles of amantadine and rimantadine in the AM2 binding pocket.
Abstract The purpose of this work was to study the mechanism of drug resistance of M2 channel proteins by analyzing the interactions between the drugs amantadine and rimantadine and M2 channel proteins (including the wild type and the three mutants V27A, S31N, and G34A) and the drug binding pathways, by use of a computational approach. Our results showed that multiple drug-binding sites were present in the M2 channel, and the trajectory of the drugs through the M2 channel was determined. A novel method was developed to investigate of free energy profiles of the ligand-protein complexes. Our work provides a new exp...
Source: European Biophysics Journal : EBJ - September 21, 2015 Category: Physics Authors: Van Nguyen H, Nguyen HT, Le LT Tags: Eur Biophys J Source Type: research

Viruses, Vol. 7, Pages 4929-4944: Clinical Implications of Antiviral Resistance in Influenza
Influenza is a major cause of severe respiratory infections leading to excessive hospitalizations and deaths globally; annual epidemics, pandemics, and sporadic/endemic avian virus infections occur as a result of rapid, continuous evolution of influenza viruses. Emergence of antiviral resistance is of great clinical and public health concern. Currently available antiviral treatments include four neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir), M2-inibitors (amantadine, rimantadine), and a polymerase inhibitor (favipiravir). In this review, we focus on resistance issues related to the use of neuram...
Source: Viruses - September 14, 2015 Category: Virology Authors: Timothy LiMartin ChanNelson Lee Tags: Review Source Type: research

New small-molecule drug design strategies for fighting resistant influenza A
Publication date: Available online 6 September 2015 Source:Acta Pharmaceutica Sinica B Author(s): Zuyuan Shen, Kaiyan Lou, Wei Wang Influenza A virus is the major cause of seasonal or pandemic flu worldwide. Two main treatment strategies–vaccination and small molecule anti-influenza drugs are currently available. As an effective vaccine usually takes at least 6 months to develop, anti-influenza small molecule drugs are more effective for the first line of protection against the virus during an epidemic outbreak, especially in the early stage. Two major classes of anti-influenza drugs currently available are adma...
Source: Acta Pharmaceutica Sinica B - September 7, 2015 Category: Cancer & Oncology Source Type: research

Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo
Publication date: Available online 10 June 2015 Source:Antiviral Research Author(s): V.V. Zarubaev , A.V. Garshinina , T.S. Tretiak , V.A. Fedorova , A.A. Shtro , A.S. Sokolova , O.I. Yarovaya , N.F. Salakhutdinov Influenza virus continues to remain one of the leading human respiratory pathogens causing significant morbidity and mortality around the globe. Due to short-term life cycle and high rate of mutations influenza virus is able to rapidly develop resistance to clinically available antivirals. This makes necessary the search and development of new drugs with different targets and mechanisms of activity. Here we rep...
Source: Antiviral Therapy - June 12, 2015 Category: Virology Source Type: research

Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo.
Abstract Influenza virus continues to remain one of the leading human respiratory pathogens causing significant morbidity and mortality around the globe. Due to short-term life cycle and high rate of mutations influenza virus is able to rapidly develop resistance to clinically available antivirals. This makes necessary the search and development of new drugs with different targets and mechanisms of activity. Here we report anti-influenza activity of camphor derivative 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol (camphecene). In in vitro experiments it inhibited influenza viruses A(H1, H1pdm09, H3 an...
Source: Antiviral Research - June 10, 2015 Category: Virology Authors: Zarubaev VV, Garshinina AV, Tretiak TS, Fedorova VA, Shtro AA, Sokolova AS, Yarovaya OI, Salakhutdinov NF Tags: Antiviral Res Source Type: research