The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Jun Wang - One of the best experts on this subject based on the ideXlab platform.
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boceprevir gc 376 and calpain inhibitors ii xii inhibit sars cov 2 viral replication by targeting the viral main protease
Cell Research, 2020Co-Authors: Michael Dominic Sacco, Brett L Hurst, Julia Alma Townsend, Tommy Szeto, Xiujun Zhang, Bart Tarbet, Michael T Marty, Yu Chen, Jun WangAbstract:A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based Enzymatic Assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the Enzymatic Assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding Assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 µM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 A resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.
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boceprevir gc 376 and calpain inhibitors ii xii inhibit sars cov 2 viral replication by targeting the viral main protease
bioRxiv, 2020Co-Authors: Michael Dominic Sacco, Brett L Hurst, Julia Alma Townsend, Tommy Szeto, Xiujun Zhang, Bart Tarbet, Michael T Marty, Yu Chen, Jun WangAbstract:A novel coronavirus SARS-CoV-2, also called novel coronavirus 2019 (nCoV-19), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.96% as of May 4, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based Enzymatic Assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the Enzymatic Assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding Assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 μM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 A resolution with three monomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.
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comparison of four commercial Enzymatic Assay kits for the analysis of organophosphate and carbamate insecticides in vegetables
Food Control, 2012Co-Authors: Jun Wang, Xintong Wang, Richard A Slawecki, Fernando RubioAbstract:Abstract Contamination of organophosphate and carbamate (OP/C) insecticides in vegetables is a serious problem in China. An increasing number of acute poisoning accidents caused by OP/C residues in vegetables have brought great concerns on food safety. Four OP/C commercial Enzymatic Assay kits were compared on their sensitivity (half maximum inhibition concentration, IC 50 ), matrix interference (i.e., background noise), accuracy (i.e., recovery) and precision (i.e., standard deviations), Assay stability, simplicity of analysis, and cost. This work is not to advocate one company's products over others. Research intention is only to provide some useful information to potential users such as various characteristics on their performance and their particular applications of the four kits. The results showed that the four kit tests have various advantages. In general, kit 1 exhibited better precision, while kit 4 had better sensitivity. Kit 1 exhibited better recovery data for the organophosphates and kit 4 had better recoveries for the carbamates than the other kits. Kit 1, kit 3 and kit 4 were more stable than kit 2 under the same temperature condition. In addition, the operation of kit 4 was the easiest. According to the performance comparison results and the cost-effective factor, kit 1 and kit 4 were more suitable for the local market.
Michael Dominic Sacco - One of the best experts on this subject based on the ideXlab platform.
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boceprevir gc 376 and calpain inhibitors ii xii inhibit sars cov 2 viral replication by targeting the viral main protease
Cell Research, 2020Co-Authors: Michael Dominic Sacco, Brett L Hurst, Julia Alma Townsend, Tommy Szeto, Xiujun Zhang, Bart Tarbet, Michael T Marty, Yu Chen, Jun WangAbstract:A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based Enzymatic Assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the Enzymatic Assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding Assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 µM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 A resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.
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boceprevir gc 376 and calpain inhibitors ii xii inhibit sars cov 2 viral replication by targeting the viral main protease
bioRxiv, 2020Co-Authors: Michael Dominic Sacco, Brett L Hurst, Julia Alma Townsend, Tommy Szeto, Xiujun Zhang, Bart Tarbet, Michael T Marty, Yu Chen, Jun WangAbstract:A novel coronavirus SARS-CoV-2, also called novel coronavirus 2019 (nCoV-19), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.96% as of May 4, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based Enzymatic Assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the Enzymatic Assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding Assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 μM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 A resolution with three monomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.
G T Maine - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a next generation direct whole blood Enzymatic Assay for hemoglobin a1c on the architect c8000 chemistry system
Clinical Chemistry and Laboratory Medicine, 2015Co-Authors: Tracy Teodoromorrison, Marcel J W Janssen, Jasper Mols, Ben H E Hendrickx, Mathieu H Velmans, Johannes Lotz, Karl J Lackner, Lieselotte Lennartz, David A Armbruster, G T MaineAbstract:BACKGROUND The utility of HbA1c for the diagnosis of type 2 diabetes requires an accurate, precise and robust test measurement system. Currently, immunoAssay and HPLC are the most popular methods for HbA1c quantification, noting however the limitations associated with some platforms, such as imprecision or interference from common hemoglobin variants. Abbott Diagnostics has introduced a fully automated direct Enzymatic method for the quantification of HbA1c from whole blood on the ARCHITECT chemistry system. METHODS Here we completed a method evaluation of the ARCHITECT HbA1c Enzymatic Assay for imprecision, accuracy, method comparison, interference from hemoglobin variants and specimen stability. This was completed at three independent clinical laboratories in North America and Europe. RESULTS The total imprecision ranged from 0.5% to 2.2% CV with low and high level control materials. Around the diagnostic cut-off of 48 mmol/mol, the total imprecision was 0.6% CV. Mean bias using reference samples from IFCC and CAP ranged from -1.1 to 1.0 mmol/mol. The Enzymatic Assay also showed excellent agreement with HPLC methods, with slopes of 1.01 and correlation coefficients ranging from 0.984 to 0.996 compared to Menarini Adams HA-8160, Bio-Rad Variant II and Variant II Turbo instruments. Finally, no significant effect was observed for erythrocyte sedimentation or interference from common hemoglobin variants in patient samples containing heterozygous HbS, HbC, HbD, HbE, and up to 10% HbF. CONCLUSIONS The ARCHITECT Enzymatic Assay for HbA1c is a robust and fully automated method that meets the performance requirements to support the diagnosis of type 2 diabetes.
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evaluation of a next generation direct whole blood Enzymatic Assay for hemoglobin a1c on the architect c8000 chemistry system
Clinical Chemistry and Laboratory Medicine, 2015Co-Authors: Tracy Teodoromorrison, Marcel J W Janssen, Jasper Mols, Ben H E Hendrickx, Mathieu H Velmans, Johannes Lotz, Karl J Lackner, Lieselotte Lennartz, David A Armbruster, G T MaineAbstract:The utility of HbA1c for the diagnosis of type 2 diabetes requires an accurate, precise and robust test measurement system. Currently, immunoAssay and HPLC are the most popular methods for HbA1c quantification, noting however the limitations associated with some platforms, such as imprecision or interference from common hemoglobin variants. Abbott Diagnostics has introduced a fully automated direct Enzymatic method for the quantification of HbA1c from whole blood on the ARCHITECT chemistry system.Here we completed a method evaluation of the ARCHITECT HbA1c Enzymatic Assay for imprecision, accuracy, method comparison, interference from hemoglobin variants and specimen stability. This was completed at three independent clinical laboratories in North America and Europe.The total imprecision ranged from 0.5% to 2.2% CV with low and high level control materials. Around the diagnostic cut-off of 48 mmol/mol, the total imprecision was 0.6% CV. Mean bias using reference samples from IFCC and CAP ranged from -1.1 to 1.0 mmol/mol. The Enzymatic Assay also showed excellent agreement with HPLC methods, with slopes of 1.01 and correlation coefficients ranging from 0.984 to 0.996 compared to Menarini Adams HA-8160, Bio-Rad Variant II and Variant II Turbo instruments. Finally, no significant effect was observed for erythrocyte sedimentation or interference from common hemoglobin variants in patient samples containing heterozygous HbS, HbC, HbD, HbE, and up to 10% HbF.The ARCHITECT Enzymatic Assay for HbA1c is a robust and fully automated method that meets the performance requirements to support the diagnosis of type 2 diabetes.
Julia Alma Townsend - One of the best experts on this subject based on the ideXlab platform.
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boceprevir gc 376 and calpain inhibitors ii xii inhibit sars cov 2 viral replication by targeting the viral main protease
Cell Research, 2020Co-Authors: Michael Dominic Sacco, Brett L Hurst, Julia Alma Townsend, Tommy Szeto, Xiujun Zhang, Bart Tarbet, Michael T Marty, Yu Chen, Jun WangAbstract:A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based Enzymatic Assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the Enzymatic Assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding Assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 µM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 A resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.
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boceprevir gc 376 and calpain inhibitors ii xii inhibit sars cov 2 viral replication by targeting the viral main protease
bioRxiv, 2020Co-Authors: Michael Dominic Sacco, Brett L Hurst, Julia Alma Townsend, Tommy Szeto, Xiujun Zhang, Bart Tarbet, Michael T Marty, Yu Chen, Jun WangAbstract:A novel coronavirus SARS-CoV-2, also called novel coronavirus 2019 (nCoV-19), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.96% as of May 4, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based Enzymatic Assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the Enzymatic Assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding Assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 μM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 A resolution with three monomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.
Brett L Hurst - One of the best experts on this subject based on the ideXlab platform.
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boceprevir gc 376 and calpain inhibitors ii xii inhibit sars cov 2 viral replication by targeting the viral main protease
Cell Research, 2020Co-Authors: Michael Dominic Sacco, Brett L Hurst, Julia Alma Townsend, Tommy Szeto, Xiujun Zhang, Bart Tarbet, Michael T Marty, Yu Chen, Jun WangAbstract:A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based Enzymatic Assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the Enzymatic Assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding Assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 µM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 A resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.
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boceprevir gc 376 and calpain inhibitors ii xii inhibit sars cov 2 viral replication by targeting the viral main protease
bioRxiv, 2020Co-Authors: Michael Dominic Sacco, Brett L Hurst, Julia Alma Townsend, Tommy Szeto, Xiujun Zhang, Bart Tarbet, Michael T Marty, Yu Chen, Jun WangAbstract:A novel coronavirus SARS-CoV-2, also called novel coronavirus 2019 (nCoV-19), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.96% as of May 4, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based Enzymatic Assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the Enzymatic Assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding Assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 μM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 A resolution with three monomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.