tamiphosphor has been researched along with Influenza--Human* in 4 studies
4 other study(ies) available for tamiphosphor and Influenza--Human
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DNA-linked inhibitor antibody assay (DIANA) as a new method for screening influenza neuraminidase inhibitors.
Influenza neuraminidase is responsible for the escape of new viral particles from the infected cell surface. Several neuraminidase inhibitors are used clinically to treat patients or stockpiled for emergencies. However, the increasing development of viral resistance against approved inhibitors has underscored the need for the development of new antivirals effective against resistant influenza strains. A facile, sensitive, and inexpensive screening method would help achieve this goal. Recently, we described a multiwell plate-based DNA-linked inhibitor antibody assay (DIANA). This highly sensitive method can quantify femtomolar concentrations of enzymes. DIANA also has been applied to high-throughput enzyme inhibitor screening, allowing the evaluation of inhibition constants from a single inhibitor concentration. Here, we report the design, synthesis, and structural characterization of a tamiphosphor derivative linked to a reporter DNA oligonucleotide for the development of a DIANA-type assay to screen potential influenza neuraminidase inhibitors. The neuraminidase is first captured by an immobilized antibody, and the test compound competes for binding to the enzyme with the oligo-linked detection probe, which is then quantified by qPCR. We validated this novel assay by comparing it with the standard fluorometric assay and demonstrated its usefulness for sensitive neuraminidase detection as well as high-throughput screening of potential new neuraminidase inhibitors. Topics: Antiviral Agents; DNA; Drug Evaluation, Preclinical; Enzyme Inhibitors; Humans; Influenza A virus; Influenza, Human; Neuraminidase; Oseltamivir; Phosphorous Acids; Reproducibility of Results; Viral Proteins | 2018 |
The additive effect of clarithromycin on influenza A infection in the elderly patients and patients with comorbid diseases.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antiviral Agents; Clarithromycin; Cohort Studies; Comorbidity; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Influenza A virus; Influenza, Human; Male; Middle Aged; Neuraminidase; Oseltamivir; Phosphorous Acids; Pneumonia; Prospective Studies; Treatment Outcome; Zanamivir | 2017 |
Kinetic, thermodynamic and structural analysis of tamiphosphor binding to neuraminidase of H1N1 (2009) pandemic influenza.
Influenza virus causes severe respiratory infections that are responsible for up to half a million deaths worldwide each year. Two inhibitors targeting viral neuraminidase have been approved to date (oseltamivir, zanamivir). However, the rapid development of antiviral drug resistance and the efficient transmission of resistant viruses among humans represent serious threats to public health. The approved influenza neuraminidase inhibitors have (oxa)cyclohexene scaffolds designed to mimic the oxonium transition state during enzymatic cleavage of sialic acid. Their active forms contain a carboxylate that interacts with three arginine residues in the enzyme active site. Recently, the phosphonate group was successfully used as an isostere of the carboxylate in oseltamivir, and the resulting compound, tamiphosphor, was identified as a highly active neuraminidase inhibitor. However, the structure of the complex of this promising inhibitor with neuraminidase has not yet been reported. Here, we analyzed the interaction of a set of oseltamivir and tamiphosphor derivatives with neuraminidase from the A/California/07/2009 (H1N1) influenza virus. We thermodynamically characterized the binding of oseltamivir carboxylate or tamiphosphor to the neuraminidase catalytic domain by protein microcalorimetry, and we determined crystal structure of the catalytic domain in complex with tamiphosphor at 1.8 Å resolution. This structural information should aid rational design of the next generation of neuraminidase inhibitors. Topics: Antiviral Agents; Catalytic Domain; Enzyme Inhibitors; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Kinetics; Neuraminidase; Oseltamivir; Pandemics; Phosphorous Acids; Protein Binding; Thermodynamics | 2016 |
A concise and flexible synthesis of the potent anti-influenza agents tamiflu and tamiphosphor.
Topics: Acetamides; Antiviral Agents; Cyclohexenes; Humans; Influenza, Human; Oseltamivir; Phosphorous Acids | 2008 |