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https://www.readbyqxmd.com/read/29214495/comparison-of-anti-influenza-virus-activity-and-pharmacokinetics-of-oseltamivir-free-base-and-oseltamivir-phosphate
#1
Jin Soo Shin, Keun Bon Ku, Yejin Jang, Yi-Seul Yoon, Daeho Shin, Oh Seung Kwon, Yun Young Go, Seong Soon Kim, Myoung Ae Bae, Meehyein Kim
Influenza viruses are major human respiratory pathogens that cause high morbidity and mortality worldwide. Currently, prophylactic vaccines and therapeutic antiviral agents are used to prevent and control influenza virus infection. Oseltamivir free base (OSV-FB), a modified generic antiviral drug of Tamiflu (oseltamivir phosphate, OSV-P), was launched in the Republic of Korea last year. Here, we examine the bioequivalence of these two compounds by assessing their antiviral efficacy in infected cells and in a mouse model...
December 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/29199545/the-inhibitory-performance-of-flavonoid-cyanidin-3-sambubiocide-against-h274y-mutation-in-h1n1-influenza-virus
#2
S Kannan, P Kolandaivel
Oseltamivir (Tamiflu) is the most accepted antiviral drug that targets the neuraminidase (NA) protein to inhibit the viral release from the host cell. Few H1N1 influenza strains with the H274Y mutation creates drug-resistance to oseltamivir. In this study, we reported flavonoid cyanidin-3-sambubiocide (C3S) compound acts as a potential inhibitor against H274Y mutation. The drug-resistance mechanism and inhibitory activity of C3S and oseltamivir against wild type (WT) and H274Y mutant type (MT) have been studied and compared based on the results of molecular docking, molecular dynamics and quantum chemical methods...
December 3, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29171473/-time-course-of-changes-in-cytokines-ifn-%C3%AE-ifn-%C3%AE-il-18-tnf-%C3%AE-in-the-treatment-of-moderate-influenza-a-h1n1-pdm09-2013-2016-with-oseltamivir-tamiflu-and-umifenovir-arbidol-alone-and-in-combination-with-kagocel
#3
A F Popov, A I Simakova, K A Dmitrenko, M Yu Shchelkanov
AIM: To assess correlation of cytokines levels and therapy regimes a relationship of the time course of changes in the cytokines IFN-γ, IFN-α, IL-18, and TNF-α to the treatment option for influenza A (H1N1) pdm09 with umifenovir (Arbidol) 800 mg/day for 5 days (n=50); oseltamivir (Tamiflu) 150 mg/day for 5 days (n=50); umifenovir (Arbidol) 800 mg/day for 5 days in combination with Kagocel 72 mg/day for 2 days.; 36 mg/day for 2 days (n=50); oseltamivir (Tamiflu) (150 mg/day for 5 days) in combination with Kagocel 72 mg/day for 2 days; 36 mg/day for 2 days (n=50)...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/29167937/novel-comprehensive-multidimensional-liquid-chromatography-approach-for-elucidation-of-the-microbosphere-of-shikimate-producing-escherichia-coli-sp1-1-pkd15-071-strain
#4
Francesco Cacciola, Domenica Mangraviti, Francesca Rigano, Paola Donato, Paola Dugo, Luigi Mondello, Hernan J Cortes
Shikimic acid is a intermediate of aromatic amino acid biosynthesis and the preferred starting material for production of the most commonly prescribed anti-influenza drug, Tamiflu. Its six-membered carbocyclic ring is adorned with several chiral centers and various functionalities, making shikimic acid a valuable chiral synthon. When microbially-produced, in addition to shikimic acid, numerous other metabolites are exported out of the cytoplasm and accumulate in the culture medium. This extracellular matrix of metabolites is referred to as the microbosphere...
November 22, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29121959/why-european-and-united-states-drug-regulators-are-not-speaking-with-one-voice-on-anti-influenza-drugs-regulatory-review-methodologies-and-the-importance-of-deep-product-reviews
#5
Shai Mulinari, Courtney Davis
BACKGROUND: Relenza represents the first neuraminidase inhibitor (NI), a class of drugs that also includes the drug Tamiflu. Although heralded as breakthrough treatments in influenza, NI efficacy has remained highly controversial. A key unsettled question is why the United States Food and Drug Administration (FDA) has approved more cautious efficacy statements in labelling than European regulators for both drugs. METHODS: We conducted a qualitative analysis of United States and European Union regulatory appraisals for Relenza to investigate the reasons for divergent regulatory interpretations, pertaining to Relenza's capacity to alleviate symptoms and reduce frequency of complications of influenza...
November 9, 2017: Health Research Policy and Systems
https://www.readbyqxmd.com/read/29118338/sialidase-inhibitors-attenuate-pulmonary-fibrosis-in-a-mouse-model
#6
Tejas R Karhadkar, Darrell Pilling, Nehemiah Cox, Richard H Gomer
Fibrosis involves increasing amounts of scar tissue appearing in a tissue, but what drives this is unclear. In fibrotic lesions in human and mouse lungs, we found extensive desialylation of glycoconjugates, and upregulation of sialidases. The fibrosis-associated cytokine TGF-β1 upregulates sialidases in human airway epithelium cells, lung fibroblasts, and immune system cells. Conversely, addition of sialidases to human peripheral blood mononuclear cells induces accumulation of extracellular TGF-β1, forming what appears to be a sialidase - TGF-β1 - sialidase positive feedback loop...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29090056/oseltamivir-tamiflu-induced-bilateral-ciliochoroidal-effusion-and-angle-closure-glaucoma-what-type-of-idiosyncratic-reaction
#7
Shahin Yazdani, Hamed Esfandiari, Sare Safi, Alireza Fatemi
PURPOSE: To report a case of bilateral acute angle closure glaucoma after one dose of oseltamivir 75 mg. CASE REPORT: A 37-year-old man with a history of influenza developed high intraocular pressure and uniformly shallow anterior chamber in both eyes, 5 hours after the first dose of oseltamivir 75 mg. The condition was managed successfully with topical cycloplegic and systemic/topical antiglaucoma medications. CONCLUSION: Since a presumed idiosyncratic reaction developed right after the first dose of the medication, it challenges the common concept of adaptive immune system involvement in this type of reaction in medication-related ciliochoroidal effusion...
October 2017: Journal of Ophthalmic & Vision Research
https://www.readbyqxmd.com/read/28977398/pharmaceutical-lobbying-and-pandemic-stockpiling-of-tamiflu-a-qualitative-study-of-arguments-and-tactics
#8
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
#9
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
#10
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
#11
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
#12
RANDOMIZED CONTROLLED TRIAL
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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