scholarly journals An integrated method for optimized identification of effective natural inhibitors against SARS-CoV-2 3CLpro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qi Liao ◽  
Ziyu Chen ◽  
Yanlin Tao ◽  
Beibei Zhang ◽  
Xiaojun Wu ◽  
...  
Keyword(s):  
Essential Role ◽  
Integrated Approach ◽  
Antiviral Drugs ◽  
Dynamics Simulation ◽  
Integrated Method ◽  
Rapid Acquisition ◽  
Chinese Herbal ◽  
Specific Effects ◽  
Antiviral Targets ◽  
Natural Inhibitors

AbstractThe current severe situation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reversed and posed great threats to global health. Therefore, there is an urgent need to find out effective antiviral drugs. The 3-chymotrypsin-like protease (3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its essential role in the regulation of virus reproduction. Here, we report an improved integrated approach to identify effective 3CLpro inhibitors from effective Chinese herbal formulas. With this approach, we identified the 5 natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. Subsequent molecular dynamics simulation additionally revealed that these molecules can be tightly bound to 3CLpro and confirmed effectiveness against COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, this optimized integrated strategy for drug screening can be utilized in the discovery of antiviral drugs to achieve rapid acquisition of drugs with specific effects on antiviral targets.

scholarly journals An integrated method for optimized identification of effective natural inhibitors against SARS-CoV-2 3CLpro

2021 ◽  
Author(s):  
Qi Liao ◽  
Ziyu Chen ◽  
Yanlin Tao ◽  
Beibei Zhang ◽  
Xiaojun Wu ◽  
...  
Keyword(s):  
Essential Role ◽  
Integrated Approach ◽  
Antiviral Drugs ◽  
Dynamics Simulation ◽  
Integrated Method ◽  
Rapid Acquisition ◽  
Chinese Herbal ◽  
Specific Effects ◽  
Antiviral Targets ◽  
Natural Inhibitors

Abstract The current severe situation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reversed and posed great threats to global health. Therefore, there is an urgent need to find out effective antiviral drugs. The 3-chymotrypsin-like protease (3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its essential role in the regulation of virus reproduction. Here, we report an improved integrated approach to identify effective 3CLpro inhibitors from effective Chinese herbal formulas. With this approach, we identified the 5 natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. Subsequent molecular dynamics simulation additionally revealed that these molecules can be tightly bound to 3CLpro and confirmed effectiveness against COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, this optimized integrated strategy for drug screening can be utilized in the discovery of antiviral drugs to achieve rapid acquisition of drugs with specific effects on antiviral targets.

scholarly journals An Integrated Method For Optimized Identification of Effective Natural Inhibitors Against SARS-CoV-2 3CLpro

2021 ◽  
Author(s):  
Qi Liao ◽  
Ziyu Chen ◽  
Yanlin Tao ◽  
Beibei Zhang ◽  
Xiaojun Wu ◽  
...  
Keyword(s):  
Essential Role ◽  
Integrated Approach ◽  
Antiviral Drugs ◽  
Dynamics Simulation ◽  
Integrated Method ◽  
Rapid Acquisition ◽  
Chinese Herbal ◽  
Specific Effects ◽  
Antiviral Targets ◽  
Natural Inhibitors

Abstract The current severe situation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reversed and posed great threats to global health. Therefore, there is an urgent need to find out effective antiviral drugs. The 3-chymotrypsin-like protease (3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its essential role in the regulation of virus reproduction. Here, we report an improved integrated approach to identify effective 3CLpro inhibitors from effective Chinese herbal formulas. With this approach, we identified the 5 natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. Subsequent molecular dynamics simulation additionally revealed that these molecules can be tightly bound to 3CLpro and confirmed effectiveness against COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, this optimized integrated strategy for drug screening can be utilized in the discovery of antiviral drugs to achieve rapid acquisition of drugs with specific effects on antiviral targets.

Use of an Integrated Approach for Analysis and Design of Turbocharged Internal Combustion Engine

2021 ◽  
Author(s):  
Thiago Ebel ◽  
Mark Anderson ◽  
Parth Pandya ◽  
Mat Perchanok ◽  
Nick Tiney ◽  
...  
Keyword(s):  
Internal Combustion Engine ◽  
Combustion Engine ◽  
Early Stage ◽  
Pressure Ratio ◽  
Integrated Approach ◽  
Internal Combustion ◽  
Operating Conditions ◽  
Dynamics Simulation ◽  
Analysis And Design ◽  
Performance Requirements

Abstract When developing a turbocharged internal combustion engine, the choice of turbocharger is usually based on designer experience and existing hardware. However, proper turbocharger design relies on matching the compressor and turbine performance to the engine requirements so that parameters such as boost and back pressure, compressor pressure ratio, and turbine inlet temperatures meet the needs of the engine without exceeding its allowable operating envelope. Therefore, the ultimate measure of a successful turbocharger design is how well it is matched to an engine across various operating conditions. This, in turn, determines whether a new turbocharger is required, or an existing solution can be used. When existing turbocharger solutions are not viable, the engine designer is at a loss on how to define a new turbocharger that meets the desired performance requirements. A common approach in industry has been to scale the performance of an existing turbocharger (compressor and turbine maps) and take these requirements for Original Equipment Manufacturers to possibly match it with a real machine. However, the assumptions made in a basic scaling process are quite simplistic and generally not satisfactory in this situation. A better approach would be to use a validated meanline model for a compressor and turbine instead, allowing to perform an actual preliminary design of such components. Such approach allows to link the engine performance requirements in a very early stage of te component design project and it guides the designer for the design decisions, such as rotor size, variable geometry nozzles, diameter, or shroud trims and others. Therefore, a feasible solution is more likely with design less iterations. This paper describes a methodology for an integrated approach to design and analyze a turbocharged internal combustion engine using commercially available state-of-the-art 1D gas dynamics simulation tool linked to two powerful turbomachinery meanline programs. The outputs of this analysis are detailed performance data of the engine and turbocharger at different engine operating conditions. Two case studies are then presented for a 10-liter diesel truck engine. The first study demonstrates how the programs are used to evaluate an existing engine and reverse engineer an existing turbocharger based only on the available performance maps. Then a second study is done using a similar approach but redesigning a new turbocharger (based on the reverse engineered one) for an increased torque output of the same engine.

scholarly journals Integrated method for the measurement of trace atmospheric bases

2011 ◽  
Vol 4 (5) ◽  
pp. 6007-6040 ◽  
Author(s):  
D. Key ◽  
J. Stihle ◽  
J.-E. Petit ◽  
C. Bonnet ◽  
L. Depernon ◽  
...  
Keyword(s):  
Nitrogen Cycle ◽  
Field Measurements ◽  
Ambient Air ◽  
Integrated Approach ◽  
Urban Park ◽  
Sampling Strategies ◽  
Road Vehicles ◽  
Integrated Method ◽  
The Many ◽  
Global Nitrogen Cycle

Abstract. Nitrogenous atmospheric bases are thought to play a key role in the global nitrogen cycle, but their sources, transport, and sinks remain poorly understood. Of the many methods available to measure such compounds in ambient air, few meet the current need of being applicable to the complete range of potential analytes and fewer still are convenient to implement using instrumentation that is standard to most laboratories. In this work, an integrated approach to measuring trace atmospheric nitrogenous bases has been developed and validated. The method uses a simple acid scrubbing step to capture and concentrate the bases as their phosphite salts, which then are derivatized and analyzed using GC/MS and/or LC/MS. The advantages of both techniques in the context of the present measurements are discussed. The approach is sensitive, selective, reproducible, as well as convenient to implement and has been validated for different sampling strategies. The limits of detection for the families of tested compounds are suitable for ambient measurement applications, as supported by field measurements in an urban park and in the exhaust of on-road vehicles.

scholarly journals An Efficient PET-MRI Medical Image Fusion based on IHS-NSCT-PCA Integrated Method

2019 ◽  
Vol 9 (2) ◽  
pp. 2073-2079
Keyword(s):  
Structural Data ◽  
Fusion Rule ◽  
Integrated Approach ◽  
Disease Diagnosis ◽  
Weighted Averaging ◽  
Fusion Algorithm ◽  
Integrated Method ◽  
Histogram Matching ◽  
Multiple Imaging ◽  
Fused Image

Merging of multiple imaging modalities leads to a single image that acquire high information content. These find useful applications in disease diagnosis and treatment planning. IHS-PCA method is a spatial domain approach for fusion that offersfinestvisibility but demands vast memory and it lacks steering information. We propose an integrated approach that incorporates NSCT combined with PCA utilizing IHS space and histogram matching. The fusion algorithm is applied on MRI with PET image and improved functional property was obtained. The IHS transform is a sharpening technique that converts multispectral image from RGB channels to Intensity Hue and Saturation independent values. Histogram matching is performed with intensity values of the two input images. Pathological details in images can be emphasized in multi-scale and multi-directions by using PCA withNSCT. Fusion rule applied is weighted averaging andprincipal components are used for dimensionality reduction. Inverse NSCT and Inverse IHS are performed so as to obtain the fused image in new RGB space. Visual and subjective investigation is compared with existing methods which demonstrate that our proposed technique gives high structural data content with high spatial and spectral resolution compared withearlier methods.

scholarly journals Integrated method for the measurement of trace nitrogenous atmospheric bases

2011 ◽  
Vol 4 (12) ◽  
pp. 2795-2807 ◽  
Author(s):  
D. Key ◽  
J. Stihle ◽  
J.-E. Petit ◽  
C. Bonnet ◽  
L. Depernon ◽  
...  
Keyword(s):  
Nitrogen Cycle ◽  
Field Measurements ◽  
Ambient Air ◽  
Integrated Approach ◽  
Urban Park ◽  
Sampling Strategies ◽  
Road Vehicles ◽  
Integrated Method ◽  
The Many ◽  
Global Nitrogen Cycle

Abstract. Nitrogenous atmospheric bases are thought to play a key role in the global nitrogen cycle, but their sources, transport, and sinks remain poorly understood. Of the many methods available to measure such compounds in ambient air, few meet the current need of being applicable to the complete range of potential analytes and fewer still are convenient to implement using instrumentation that is standard to most laboratories. In this work, an integrated approach to measuring trace, atmospheric, gaseous nitrogenous bases has been developed and validated. The method uses a simple acid scrubbing step to capture and concentrate the bases as their phosphite salts, which then are derivatized and analyzed using GC/MS and/or LC/MS. The advantages of both techniques in the context of the present measurements are discussed. The approach is sensitive, selective, reproducible, as well as convenient to implement and has been validated for different sampling strategies. The limits of detection for the families of tested compounds are suitable for ambient measurement applications (e.g., methylamine, 1 pptv; ethylamine, 2 pptv; morpholine, 1 pptv; aniline, 1 pptv; hydrazine, 0.1 pptv; methylhydrazine, 2 pptv), as supported by field measurements in an urban park and in the exhaust of on-road vehicles.

Phenylbenzopyrone of flavonoids as a potential scaffold to prevent SARS-CoV-2 replication by inhibiting its MPRO main protease

2021 ◽  
Vol 22 ◽  
Author(s):  
Angamba Meetei Potshangbam ◽  
Potshangbam Nongdam ◽  
A. Kiran Kumar ◽  
R.S. Rathore
Keyword(s):  
Antiviral Drugs ◽  
Dynamics Simulation ◽  
Compound Libraries ◽  
Main Protease ◽  
Enterovirus A71 ◽  
Short Period ◽  
Novel Coronavirus ◽  
Effective Drugs ◽  
Drug Leads ◽  
Better Than

Background: In December 2019, an outbreak of a pneumonia-like illness, Coronavirusdisease-2019 (COVID-19), originating from Wuhan, China was linked to novel coronavirus, now termed SARS-CoV-2. Unfortunately, no effective drugs or vaccines have been reported yet. The main protease (MPRO) remains the most validated pharmacological target for the design and discovery of inhibitors. Objective: The purpose of the study was to find a prospective natural scaffold as an inhibitor for MPRO main protease in SARS-CoV-2 and compare it with repurposed antiviral drugs lopinavir and nelflinavir. Methods: Natural compound libraries were screened for potential scaffold against MPRO main protease. Molecular dynamics simulation, MM-GBSA and principle component analyses of enzyme-ligand complexes were carried out with the top-ranking hits and compared with the repurposed antiviral drugs lopinavir and nelfinavir. Results: The structure-based virtual screening indicated phenylbenzopyrone of flavonoids as one of the top-ranking scaffolds that have the potential to inhibit the main protease with O-glycosidic form performing better than corresponding aglyconic form. Simulation studies indicated that glycosidic form of flavonoid as more suitable inhibitor with compounds rutin, procyanidin B6, baicalin and galloylquercetin, demonstrating high affinity and stability, and rutin emerging as one of the best candidate compound. Interestingly, rutin was reported to have inhibitory activity against similar protease (3Cprotease of enterovirus A71) as well as implicated in lung fibrosis. Conclusion: The present study displaying flavonoids, possessing a potential scaffold for inhibiting main protease activity for all betacoronavirus is an attempt to provide new and safe drug leads within a reasonably short period.

scholarly journals Material Analysis and Molecular Dynamics Simulation for Cavitation Erosion and Corrosion Suppression in Water Hydraulic Valves

Materials ◽  
2020 ◽  
Vol 13 (2) ◽  
pp. 453 ◽  
Author(s):  
Masoud Kamoleka Mlela ◽  
He Xu ◽  
Feng Sun ◽  
Haihang Wang ◽  
Gabriel Donald Madenge
Keyword(s):  
Molecular Dynamics ◽  
Md Simulation ◽  
Essential Role ◽  
Corrosion Inhibitors ◽  
Cavitation Erosion ◽  
Dynamics Simulation ◽  
Preference Ranking ◽  
Water Hydraulics ◽  
The Impact ◽  
Hydraulic Valves

In the milestone of straggling to make water hydraulics more advantageous, the choice of coating polymer for water hydraulics valves plays an essential role in alleviating the impact of cavitation erosion and corrosion, and this is a critical task for designers. Fulfilling the appropriate selection, we conflicted properties that are vital for erosion and corrosion inhibitors, as well as the tribology in the sense of coefficient of friction. This article aimed to choose the best alternative polymer for coating on the selected substrate, that is, Cr2O3, Al2O3, Ti2O3. By applying PROMETHEE (Preference Ranking Organization Method for Enrichment Evaluations), the best polymer obtained with an analyzed performance attribute is Polytetrafluoroethylene (PTFE) that comes up with higher outranking (0.5932052). A Molecular Dynamics (MD) simulation was conducted to identify the stronger bonding with the regards of the better cleave plane between Polytetrafluoroethylene (PTFE) and the selected substrate. Polytetrafluoroethylene (PTFE)/Al2O3 cleaved in (010) plane was observed to be the strongest bond in terms of binding energy (3188 kJ/mol) suitable for further studies.

scholarly journals Fast four-dimensional tensile test monitored via X-ray computed tomography: Elastoplastic identification from radiographs

2019 ◽  
Vol 54 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Clément Jailin ◽  
Ante Buljac ◽  
Amine Bouterf ◽  
François Hild ◽  
Stéphane Roux
Keyword(s):  
Tensile Test ◽  
Correlation Method ◽  
Integrated Approach ◽  
Companion Paper ◽  
Constitutive Law ◽  
Free Form ◽  
Model Parameters ◽  
Displacement Fields ◽  
Integrated Method ◽  
Ductile Behavior

A projection-based digital volume correlation method (presented in a companion paper) is extended to an integrated approach for the calibration of an elastoplastic law based on a single radiograph per loading step. Instead of following a two-step sequential procedure (i.e. first, measurement of the displacement field; second, identification), the integrated method aims at identifying few model parameters directly from the gray-level projections. The analysis of an in situ tensile test composed of 127 loading steps performed in 6 min is presented. An isotropic elastoplastic constitutive law with free-form hardening behavior (i.e. controlled by only eight parameters) is identified and shows a ductile behavior (up to 6.3% strain before failure). A large improvement on the residual quality is shown and validates the proposed model and procedure. The obtained displacement fields are similar to those measured with no mechanical integration. A different parameterization of the constitutive law provides a very close result, thereby assessing the robustness of the procedure.

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