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https://www.readbyqxmd.com/read/28977398/pharmaceutical-lobbying-and-pandemic-stockpiling-of-tamiflu-a-qualitative-study-of-arguments-and-tactics
#1
Andreas Vilhelmsson, Shai Mulinari
Background: Little is known about how pharmaceutical companies lobby authorities or experts regarding procurement or the use of vaccines and antivirals. This paper investigates how members of Denmark's pandemic planning committee experienced lobbying efforts by Roche, manufacturer of Tamiflu, the antiviral that was stockpiled before the 2009 A(H1N1) pandemic. Methods: Analysis of interviews with six of seven members of the Danish core pandemic committee, supplemented with documentary analysis...
August 9, 2017: Journal of Public Health
https://www.readbyqxmd.com/read/28962609/novel-technologies-combined-with-traditional-metabolic-engineering-strategies-facilitate-the-construction-of-shikimate-producing-escherichia-coli
#2
REVIEW
Pengfei Gu, Xiangyu Fan, Quanfeng Liang, Qingsheng Qi, Qiang Li
Shikimate is an important intermediate in the aromatic amino acid pathway, which can be used as a promising building block for the synthesis of biological compounds, such as neuraminidase inhibitor Oseltamivir (Tamiflu(®)). Compared with traditional methods, microbial production of shikimate has the advantages of environmental friendliness, low cost, feed stock renewability, and product selectivity and diversity, thus receiving more and more attentions. The development of metabolic engineering allows for high-efficiency production of shikimate of Escherichia coli by improving the intracellular level of precursors, blocking downstream pathway, releasing negative regulation factors, and overexpressing rate-limiting enzymes...
September 29, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28885544/chemical-genomics-approach-leads-to-the-identification-of-hesperadin-an-aurora-b-kinase-inhibitor-as-a-broad-spectrum-influenza-antiviral
#3
Yanmei Hu, Jiantao Zhang, Rami Musharrafieh, Raymond Hau, Chunlong Ma, Jun Wang
Influenza viruses are respiratory pathogens that are responsible for annual influenza epidemics and sporadic influenza pandemics. Oseltamivir (Tamiflu(®)) is currently the only FDA-approved oral drug that is available for the prevention and treatment of influenza virus infection. However, its narrow therapeutic window, coupled with the increasing incidence of drug resistance, calls for the next generation of influenza antivirals. In this study, we discovered hesperadin, an aurora B kinase inhibitor, as a broad-spectrum influenza antiviral through forward chemical genomics screening...
September 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28771833/chirality-sensing-of-bioactive-compounds-with-amino-alcohol-unit-via-circular-dichroism
#4
Marcin Górecki, Grażyna Groszek, Jadwiga Frelek
The aim of the present work was to test various chiroptical techniques, including in particular the in situ dirhodium methodology, to assign the absolute configuration of 1,2- and 1,3-amino alcohols. As models, we selected mainly compounds that have both an additional strongly absorbing and interfering chromophoric system and application in medicinal chemistry. Determination of the absolute configuration (AC) of the tested molecules such as cinchona alkaloids, Tamiflu, and others was carried out using a combination of electronic and vibrational circular dichroism (ECD, VCD) spectroscopy...
October 2017: Chirality
https://www.readbyqxmd.com/read/28737128/bioequivalence-of-two-oseltamivir-formulations-in-healthy-chinese-volunteers%C3%A2
#5
Yun-Lei Yun, Shou-Hong Gao, Yan Wen, Zhi-Peng Wang, Hai-Jun Miao, Wan-Sheng Chen
BACKGROUND: The aim of this study was to compare the bioavailability of a new generic formulation of oseltamivir 75-mg capsule (test) and a branded formulation Tamiflu<sup>®</sup> (reference) to meet regulatory criteria for marketing the test product in healthy Chinese male volunteers. METHODS: This single-dose, randomized-sequence, open-label, two-period crossover study was conducted in fasted healthy Chinese male volunteers, who first received a single oral dose of the test or reference formulation with a 7-day washout period, and then the alternative formulation...
September 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28687536/what-makes-an-essential-medicine-who-s-new-list-focuses-on-antibiotic-resistance-adds-expensive-drugs-and-downgrades-tamiflu
#6
Michael McCarthy
No abstract text is available yet for this article.
July 7, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28535854/influenza-a-world-of-discoveries-outbreaks-and-controversy
#7
Wendy S Barclay
Working in an area such as influenza is a free ticket into science communication, a pathway aided amply by the amazing evolutionary powers of the virus; regular outbreaks keep the media engaged and the audience keen. Everyone has heard of flu, and they probably already have an opinion: 'I don't take the vaccine, it gives me the flu anyway.' 'Didn't the government waste loads of money on that Tamiflu drug that doesn't work?' 'I've never had flu because I eat a banana every day and sleep with a boiled onion when I've sat next to someone on the train who was coughing...
May 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28500071/activated-microglia-desialylate-and-phagocytose-cells-via-neuraminidase-galectin-3-and-mer-tyrosine-kinase
#8
Koji Nomura, Anna Vilalta, David H Allendorf, Tamara C Hornik, Guy C Brown
Activated microglia can phagocytose dying, stressed, or excess neurons and synapses via the phagocytic receptor Mer tyrosine kinase (MerTK). Galectin-3 (Gal-3) can cross-link surface glycoproteins by binding galactose residues that are normally hidden below terminal sialic acid residues. Gal-3 was recently reported to opsonize cells via activating MerTK. We found that LPS-activated BV-2 microglia rapidly released Gal-3, which was blocked by calcineurin inhibitors. Gal-3 bound to MerTK on microglia and to stressed PC12 (neuron-like) cells, and it increased microglial phagocytosis of PC12 cells or primary neurons, which was blocked by inhibition of MerTK...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28457075/comparative-characteristics-of-the-2009-pandemic-influenza-a-h1n1-virus-and-2010-2011-seasonal-influenza-in-pediatric-patients
#9
Najwan Nasrallah, Yael Shachor-Meyouhas, Zipi Kra-Oz, Tania Mashiach, Moran Szwarcwort-Cohen, Eynat Shafran, Imad Kassis
BACKGROUND: In March 2009 the pandemic influenza A (H1N1) strain was identified. The disease initially appeared to be accompanied by complications and high mortality rates. It became an endemic virus during the influenza season in our region, along with the classical seasonal H3N2. OBJECTIVES: To identify the burden of pandemic influenza, its effect in pediatric patients, and complicated hospitalizations, compared to seasonal influenza years after the pandemic. METHODS: A retrospective observational study was conducted at a tertiary hospital...
December 2016: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/28433777/design-and-expeditious-synthesis-of-organosilanes-as-potent-antivirals-targeting-multidrug-resistant-influenza-a-viruses
#10
Yanmei Hu, Yuanxiang Wang, Fang Li, Chunlong Ma, Jun Wang
The efficacy of current influenza vaccines and small molecule antiviral drugs is curtailed by the emerging of multidrug-resistant influenza viruses. As resistance to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu), continues to rise, there is a clear need to develop the next-generation of antiviral drugs. Since more than 95% of current circulating influenza A viruses carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel represents an attractive target for the development of broad-spectrum antivirals...
July 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28416546/anti-influenza-activity-of-a-bacillus-subtilis-probiotic-strain
#11
Darya Starosila, Svetlana Rybalko, Ludmila Varbanetz, Naila Ivanskaya, Iryna Sorokulova
Among Bacillus bacteria, B. subtilis is the species that produces the most antimicrobial compounds. In this study, we analyzed the activity of probiotic strain B. subtilis 3 against the influenza virus. The antiviral effect of this strain has been demonstrated in vitro and in vivo A new peptide, P18, produced by the probiotic strain was isolated, purified, chemically synthesized, and characterized. Cytotoxicity studies demonstrated no toxic effect of P18 on Madin-Darby canine kidney (MDCK) cells, even at the highest concentration tested (100 μg/ml)...
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28377100/the-mek-inhibitor-ci-1040-displays-a-broad-anti-influenza-virus-activity-in%C3%A2-vitro-and-provides-a-prolonged-treatment-window-compared-to-standard-of-care-in%C3%A2-vivo
#12
Emanuel Haasbach, Christin Müller, Christina Ehrhardt, Andre Schreiber, Stephan Pleschka, Stephan Ludwig, Oliver Planz
Influenza viruses (IV) continue to pose an imminent threat to human welfare. Yearly re-occurring seasonal epidemic outbreaks and pandemics with high mortality can occur. Besides vaccination against a limited number of viral strains only a few antiviral drugs are available, which are losing their effectiveness as more and more IV strains become resistant. Thus, new antiviral approaches that omit IV resistance are urgently needed. Here, the dependency on the cellular Raf/MEK/ERK signaling pathway for IV replication opens a new perspective...
June 2017: Antiviral Research
https://www.readbyqxmd.com/read/28337082/pharmacokinetics-of-peramivir-in-an-adolescent-patient-receiving-continuous-venovenous-hemodiafiltration
#13
Ryan C Dillon, Robert Witcher, Jeffrey J Cies, Wayne S Moore, Arun Chopra
Critically ill patients requiring renal replacement therapy commonly experience pharmacokinetic alterations. This case report describes the pharmacokinetics of peramivir (Rapivab, BioCryst Pharmaceuticals, Inc, Durham, NC), the first US Food and Drug Administration-approved intravenous neuraminidase inhibitor for the treatment of influenza, in an adolescent patient receiving continuous renal replacement therapy (CRRT). A 49.5-kg, 17-year-old Caucasian female presented with fever, cough, and persistent hypoxia...
January 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/28315686/crystal-structure-of-the-catalytic-domain-of-clostridium-perfringens-neuraminidase-in-complex-with-a-non-carbohydrate-based-inhibitor-2-cyclohexylamino-ethanesulfonic-acid
#14
Youngjin Lee, Hyung-Seop Youn, Jung-Gyu Lee, Jun Yop An, Kyoung Ryoung Park, Jung Youn Kang, Young Bae Ryu, Mi Sun Jin, Ki Hun Park, Soo Hyun Eom
Anti-bacterial and anti-viral neuraminidase agents inhibit neuraminidase activity catalyzing the hydrolysis of terminal N-acetylneuraminic acid (Neu5Ac) from glycoconjugates and help to prevent the host pathogenesis that lead to fatal infectious diseases including influenza, bacteremia, sepsis, and cholera. Emerging antibiotic and drug resistances to commonly used anti-neuraminidase agents such as oseltamivir (Tamiflu) and zanamivir (Relenza) have highlighted the need to develop new anti-neuraminidase drugs...
April 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28188897/survival-biases-lead-to-flawed-conclusions-in-observational-treatment-studies-of-influenza-patients
#15
Martin Wolkewitz, Martin Schumacher
BACKGROUND AND OBJECTIVE: Several observational studies reported that Oseltamivir (Tamiflu) reduced mortality in infected and hospitalized patients. Because of the restriction of observation to hospital stay and time-dependent treatment assignment, such findings were prone to common types of survival bias (length, time-dependent and competing risk bias). METHODS: British hospital data from the Influenza Clinical Information Network (FLU-CIN) study group were used which included 1,391 patients with confirmed pandemic influenza A/H1N1 2009 infection...
April 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28155963/stereoisomers-of-oseltamivir-synthesis-in-silico-prediction-and-biological-evaluation
#16
Viktória Hajzer, Roman Fišera, Attila Latika, Július Durmis, Jakub Kollár, Vladimír Frecer, Zuzana Tučeková, Stanislav Miertuš, František Kostolanský, Eva Varečková, Radovan Šebesta
Oseltamivir is an important antiviral drug, which possess three chirality centers in its structure. From eight possible stereoisomers, only two have been synthesized and evaluated so far. We describe herein the stereoselective synthesis, computational activity prediction and biological testing of another three diastereoisomers of oseltamivir. These isomers have been synthesized using stereoselective organocatalytic Michael addition, cyclization and reduction. Their binding to viral neuraminidase N1 of influenza A virus was evaluated by quantum-chemical calculations and their anti-influenza activities were tested by an in vitro virus-inhibition assay...
February 3, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28102191/a-broadly-protective-therapeutic-antibody-against-influenza-b-virus-with-two-mechanisms-of-action
#17
Ning Chai, Lee R Swem, Summer Park, Gerald Nakamura, Nancy Chiang, Alberto Estevez, Rina Fong, Lynn Kamen, Elviza Kho, Mike Reichelt, Zhonghua Lin, Henry Chiu, Elizabeth Skippington, Zora Modrusan, Jeremy Stinson, Min Xu, Patrick Lupardus, Claudio Ciferri, Man-Wah Tan
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/27997573/genetic-characterization-of-circulating-2015-a-h1n1-pdm09-influenza-viruses-from-eastern-india
#18
Anupam Mukherjee, Mukti Kant Nayak, Shanta Dutta, Samiran Panda, Biswa Ranjan Satpathi, Mamta Chawla-Sarkar
In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015...
2016: PloS One
https://www.readbyqxmd.com/read/27966711/development-of-a-point-of-care-diagnostic-for-influenza-detection-with-antiviral-treatment-effectiveness-indication
#19
Richard C Murdock, Karen M Gallegos, Joshua A Hagen, Nancy Kelley-Loughnane, Alison A Weiss, Ian Papautsky
Currently, diagnosis of influenza is performed either through tedious polymerase chain reaction (PCR) or through rapid antigen detection assays. The rapid antigen detection assays available today are highly specific but not very sensitive, and most importantly, lack the ability to show if the strain of influenza detected is susceptible to antiviral agents, such as Tamiflu and Relenza. The ability to rapidly determine if a patient has an infectious disease and what type of treatment the infection will respond to, would significantly reduce the treatment decision time, shorten the impact of symptoms, and minimize transfer to others...
January 17, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/27924780/activity-of-ergoferon-against-lethal-influenza-a-h3n2-virus-infection-in-mice
#20
Maria A Skarnovich, Alexandra G Emelyanova, Nataliia V Petrova, Alena A Borshcheva, Evgeniy A Gorbunov, Oleg Yu Mazurkov, Maksim O Skarnovich, Sergey A Tarasov, Larisa N Shishkina, Oleg I Epstein
BACKGROUND: The influenza A virus accounts for serious annual viral upper respiratory tract infections. It is constantly able to modify its antigenic structure, thus evading host defence mechanisms. Moreover, currently available anti-influenza agents have a rather limited application, emphasizing the further need for new effective treatments. One of them is ergoferon, a drug containing combined polyclonal antibodies - anti-interferon gamma, anti-CD4 receptor and anti-histamine - in released-active form...
2017: Antiviral Therapy
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