The Experts below are selected from a list of 948 Experts worldwide ranked by ideXlab platform
Hung Nguyen - One of the best experts on this subject based on the ideXlab platform.
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Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth Reaction Path Generation (SRPG) Method.
Journal of chemical information and modeling, 2015Co-Authors: Hung Nguyen, Tien Tran, Yoshifumi Fukunishi, Junichi Higo, Haruki NakamuraAbstract:Assessment of accurate drug binding affinity to a protein remains a challenge for in silico drug development. In this research, we used the smooth reaction path generation (SRPG) method to calculate binding free energies and determine potential of mean forces (PMFs) along the smoothed dissociation paths of influenza A neuraminidase and its variants with oseltamivir (Tamiflu) and zanamivir (Relenza) inhibitors. With the gained results, we found that the binding free energies of neuraminidase A/H5N1 in WT and two mutants (including H274Y and N294S) with oseltamivir and zanamivir show good agreement with experimental results. Additionally, the thermodynamic origin of the drug resistance of the mutants was also discussed from the PMF profiles.
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Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth Reaction Path Generation (SRPG) Method
2015Co-Authors: Hung Nguyen, Tien Tran, Yoshifumi Fukunishi, Junichi Higo, Haruki NakamuraAbstract:Assessment of accurate drug binding affinity to a protein remains a challenge for in silico drug development. In this research, we used the smooth reaction path generation (SRPG) method to calculate binding free energies and determine potential of mean forces (PMFs) along the smoothed dissociation paths of influenza A neuraminidase and its variants with oseltamivir (Tamiflu) and zanamivir (Relenza) inhibitors. With the gained results, we found that the binding free energies of neuraminidase A/H5N1 in WT and two mutants (including H274Y and N294S) with oseltamivir and zanamivir show good agreement with experimental results. Additionally, the thermodynamic origin of the drug resistance of the mutants was also discussed from the PMF profiles
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Top-hits for A/H1N1 Identified by Virtual Screening Using Ensemble-based Docking.
PLoS Currents, 2009Co-Authors: Hung Nguyen, Thanh N. TruongAbstract:A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of the bird flu H5N1, an effective means to quickly identify top candidates for use against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI diversity set which bind best to H5N1 neuraminidase. These compounds serve as viable candidates for docking against the H1N1pdm neuraminidase, using ensembles extracted from molecular dynamics simulations of the H1N1pdm system. The ranking order of these top candidates was found to be different from the previously published results for H5N1. The results indicated that the Oseltamivir (Tamiflu) and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six drug candidates were found to bind more effectively to H1N1pdm neuraminidase than Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also provided.
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Top-hits for H1N1pdm Identified by Virtual Screening Using Ensemble-based Docking.
PLoS currents, 2009Co-Authors: Hung Nguyen, Thanh N. TruongAbstract:A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of the bird flu H5N1, an effective means to quickly identify top candidates for use against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI diversity set which bind best to H5N1 neuraminidase. These compounds serve as viable candidates for docking against the H1N1pdm neuraminidase, using ensembles extracted from molecular dynamics simulations of the H1N1pdm system. The ranking order of these top candidates was found to be different from the previously published results for H5N1. The results indicated that the Oseltamivir (Tamiflu) and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six drug candidates were found to bind more effectively to H1N1pdm neuraminidase than Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also provided.
Haruki Nakamura - One of the best experts on this subject based on the ideXlab platform.
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Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth Reaction Path Generation (SRPG) Method.
Journal of chemical information and modeling, 2015Co-Authors: Hung Nguyen, Tien Tran, Yoshifumi Fukunishi, Junichi Higo, Haruki NakamuraAbstract:Assessment of accurate drug binding affinity to a protein remains a challenge for in silico drug development. In this research, we used the smooth reaction path generation (SRPG) method to calculate binding free energies and determine potential of mean forces (PMFs) along the smoothed dissociation paths of influenza A neuraminidase and its variants with oseltamivir (Tamiflu) and zanamivir (Relenza) inhibitors. With the gained results, we found that the binding free energies of neuraminidase A/H5N1 in WT and two mutants (including H274Y and N294S) with oseltamivir and zanamivir show good agreement with experimental results. Additionally, the thermodynamic origin of the drug resistance of the mutants was also discussed from the PMF profiles.
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Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth Reaction Path Generation (SRPG) Method
2015Co-Authors: Hung Nguyen, Tien Tran, Yoshifumi Fukunishi, Junichi Higo, Haruki NakamuraAbstract:Assessment of accurate drug binding affinity to a protein remains a challenge for in silico drug development. In this research, we used the smooth reaction path generation (SRPG) method to calculate binding free energies and determine potential of mean forces (PMFs) along the smoothed dissociation paths of influenza A neuraminidase and its variants with oseltamivir (Tamiflu) and zanamivir (Relenza) inhibitors. With the gained results, we found that the binding free energies of neuraminidase A/H5N1 in WT and two mutants (including H274Y and N294S) with oseltamivir and zanamivir show good agreement with experimental results. Additionally, the thermodynamic origin of the drug resistance of the mutants was also discussed from the PMF profiles
Thanh N. Truong - One of the best experts on this subject based on the ideXlab platform.
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Top-hits for A/H1N1 Identified by Virtual Screening Using Ensemble-based Docking.
PLoS Currents, 2009Co-Authors: Hung Nguyen, Thanh N. TruongAbstract:A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of the bird flu H5N1, an effective means to quickly identify top candidates for use against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI diversity set which bind best to H5N1 neuraminidase. These compounds serve as viable candidates for docking against the H1N1pdm neuraminidase, using ensembles extracted from molecular dynamics simulations of the H1N1pdm system. The ranking order of these top candidates was found to be different from the previously published results for H5N1. The results indicated that the Oseltamivir (Tamiflu) and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six drug candidates were found to bind more effectively to H1N1pdm neuraminidase than Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also provided.
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Top-hits for H1N1pdm Identified by Virtual Screening Using Ensemble-based Docking.
PLoS currents, 2009Co-Authors: Hung Nguyen, Thanh N. TruongAbstract:A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of the bird flu H5N1, an effective means to quickly identify top candidates for use against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI diversity set which bind best to H5N1 neuraminidase. These compounds serve as viable candidates for docking against the H1N1pdm neuraminidase, using ensembles extracted from molecular dynamics simulations of the H1N1pdm system. The ranking order of these top candidates was found to be different from the previously published results for H5N1. The results indicated that the Oseltamivir (Tamiflu) and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six drug candidates were found to bind more effectively to H1N1pdm neuraminidase than Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also provided.
Leungsharon Shui Yee - One of the best experts on this subject based on the ideXlab platform.
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a proof of principle setup for delivery of Relenza zanamivir inhalation powder to intubated patients
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2016Co-Authors: Leungsharon Shui YeeAbstract:Abstract Background: A fatal incident was reported when a mechanical ventilated patient received nebulization of a reconstituted Relenza® formulation. We propose a delivery system to introduce Relenza and other inhalation dry powders to intubated patients to avoid accidental fatalities in the future. Methods: This is a bench study demonstrating the feasibility of a delivery system to introduce dry powder of Relenza to intubated patients. A dry powder inhaler placed within a delivery chamber was actuated by compressing a ventilation bag to disperse powder into a tracheal tube. The performance of two inhalers, a Diskhaler® and an Osmohaler™, were compared. The effects of the length and size of the tracheal tube on the powder output and sizing of emitted powder were investigated using the more efficient Osmohaler™. Results: The efficiency of Osmohaler in delivering Relenza to the distal end [delivered dose=30.2±0.2% and fine particle fraction (FPF)=14.5±1.7%] was significantly higher than the Diskhaler (deli...
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A Proof-of-Principle Setup for Delivery of Relenza(®) (Zanamivir) Inhalation Powder to Intubated Patients.
Journal of aerosol medicine and pulmonary drug delivery, 2015Co-Authors: Leungsharon Shui Yee, Parumasivamthaigarajan, Tangpatricia, Chanhak-kimAbstract:Abstract Background: A fatal incident was reported when a mechanical ventilated patient received nebulization of a reconstituted Relenza® formulation. We propose a delivery system to introduce Relenza and other inhalation dry powders to intubated patients to avoid accidental fatalities in the future. Methods: This is a bench study demonstrating the feasibility of a delivery system to introduce dry powder of Relenza to intubated patients. A dry powder inhaler placed within a delivery chamber was actuated by compressing a ventilation bag to disperse powder into a tracheal tube. The performance of two inhalers, a Diskhaler® and an Osmohaler™, were compared. The effects of the length and size of the tracheal tube on the powder output and sizing of emitted powder were investigated using the more efficient Osmohaler™. Results: The efficiency of Osmohaler in delivering Relenza to the distal end [delivered dose=30.2±0.2% and fine particle fraction (FPF)=14.5±1.7%] was significantly higher than the Diskhaler (deli...
Peter R Byron - One of the best experts on this subject based on the ideXlab platform.
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In Vitro Tests for Aerosol Deposition II: IVIVCs for Different Dry Powder Inhalers in Normal Adults
Journal of aerosol medicine and pulmonary drug delivery, 2012Co-Authors: Renishkumar Delvadia, Michael Hindle, P. Worth Longest, Peter R ByronAbstract:Abstract Background: A new in vitro test method for dry powder inhalers (DPIs) was recently found to be predictive of the published in vivo results for Budelin Novolizer. The present study was intended to assess the method's robustness by evaluating correlations between average drug deposition in vitro and in vivo from five different DPIs. Methods: In vitro drug deposition from five marketed DPIs was assessed in a realistic physical airway model of a “medium” sized adult in an experimental setup that allowed deposition to be characterized regionally for carefully selected simulated air flow rate versus time profiles. The DPIs studied were Spiriva® HandiHaler®, Relenza® Diskhaler®, Salbutamol Easyhaler®, Pulmicort® Turbuhaler®, and Foradil® Aerolizer®. In vitro regional deposition results were compared with those reported in the literature in order to create in vitro–in vivo correlations (IVIVCs) for each inhaler. Results: Mean percent total lung deposition (TLD±SD) in vitro for Spiriva HandiHaler, Relenza...
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cascade impactor practice for a high dose dry powder inhaler at 90 l min ngi versus modified 6 stage and 8 stage aci
Journal of Pharmaceutical Sciences, 2009Co-Authors: Akihiko Kamiya, Masahiro Sakagami, Peter R ByronAbstract:Abstract The compendial methods of particle size distribution (PSD) profile determination for dry powder inhalers (DPIs) were compared between the Next Generation Pharmaceutical Impactor (NGI) and the Andersen Cascade Impactor (ACI). Relenza® Rotadisk® (zanamivir) and Diskhaler® was used as a model DPI and sampled into each impactor via its preseparator (PS), at 90 L/min under various protocols. In the NGI, silicone coating was shown to be indispensable to prevent or minimize particle bounce and reentrainment, and to reduce wall losses to the levels acceptable to the compendia (5%). In contrast, the ACI exceeded this 5% limit, regardless of coating, implying different wall loss mechanisms from the NGI. Particle bounce occurred in both impactors, inaccurately undersizing the PSD profiles for Relenza®, unless the collection surfaces were coated or an increased number of doses were employed. Hence, the PSD profile for Relenza® following single dose collection in the stage-coated NGI was the most accurate. In contrast, the use of the ACI and its PS for Relenza® at 90 L/min suffered from several problems, even though the poorly designed PS still resulted in consistent impactor dose and PSD profiles, compared to those obtained from the NGI and its PS.