Neuraminidase inhibition improves endothelial function in diabetic mice
Am J Physiol Heart Circ Physiol. 2023 Oct 6. doi: 10.1152/ajpheart.00337.2023. Online ahead of print.ABSTRACTNeuraminidases cleave sialic acids from glycocalyx structures and plasma neuraminidase activity is elevated in type 2 diabetes (T2D). Therefore, we hypothesize circulating neuraminidase degrades the endothelial glycocalyx and diminishes flow-mediated dilation (FMD), while its inhibition restores shear mechanosensation and endothelial function in T2D settings. We found that compared with controls, T2D subjects have higher plasma neuraminidase activity, reduced plasma nitrite concentrations, and diminished FMD. Ex viv...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 6, 2023 Category: Physiology Authors: Christopher A Foote Francisco I Ramirez-Perez James A Smith Thaysa Ghiarone Mariana Morales-Quinones Neil J McMillan Marc A Augenreich Gavin Power Katherine Burr Annayya Aroor Shawn B Bender Camila Manrique-Acevedo Jaume Padilla Luis A Martinez-Lemus Source Type: research
Molecules, Vol. 28, Pages 6678: Pharmacoinformatics and Breed-Based De Novo Hybridization Studies to Develop New Neuraminidase Inhibitors as Potential Anti-Influenza Agents
A. Kawsar
Influenza represents a profoundly transmissible viral ailment primarily afflicting the respiratory system. Neuraminidase inhibitors constitute a class of antiviral therapeutics employed in the management of influenza. These inhibitors impede the liberation of the viral neuraminidase protein, thereby impeding viral dissemination from the infected cell to host cells. As such, neuraminidase has emerged as a pivotal target for mitigating influenza and its associated complications. Here, we apply a de novo hybridization approach based on a breed-centric methodology to elucidate novel neuraminidase inhibitors. The ...
Source: Molecules - September 18, 2023 Category: Chemistry Authors: Bourougaa Lotfi Ouassaf Mebarka Bader Y. Alhatlani Emad M. Abdallah Sarkar M. A. Kawsar Tags: Article Source Type: research
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by th...
Source: Antiviral Research - September 17, 2023 Category: Virology Authors: Rongyuan Gao Philippe Noriel Q Pascua Ha T Nguyen Anton Chesnokov Chloe Champion Vasiliy P Mishin Dave E Wentworth Larisa V Gubareva Source Type: research
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by th...
Source: Antiviral Research - September 17, 2023 Category: Virology Authors: Rongyuan Gao Philippe Noriel Q Pascua Ha T Nguyen Anton Chesnokov Chloe Champion Vasiliy P Mishin Dave E Wentworth Larisa V Gubareva Source Type: research
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by th...
Source: Cell Research - September 17, 2023 Category: Cytology Authors: Rongyuan Gao Philippe Noriel Q Pascua Ha T Nguyen Anton Chesnokov Chloe Champion Vasiliy P Mishin Dave E Wentworth Larisa V Gubareva Source Type: research
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by th...
Source: Antiviral Research - September 17, 2023 Category: Virology Authors: Rongyuan Gao Philippe Noriel Q Pascua Ha T Nguyen Anton Chesnokov Chloe Champion Vasiliy P Mishin Dave E Wentworth Larisa V Gubareva Source Type: research
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by th...
Source: Antiviral Research - September 17, 2023 Category: Virology Authors: Rongyuan Gao Philippe Noriel Q Pascua Ha T Nguyen Anton Chesnokov Chloe Champion Vasiliy P Mishin Dave E Wentworth Larisa V Gubareva Source Type: research
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by th...
Source: Antiviral Research - September 17, 2023 Category: Virology Authors: Rongyuan Gao Philippe Noriel Q Pascua Ha T Nguyen Anton Chesnokov Chloe Champion Vasiliy P Mishin Dave E Wentworth Larisa V Gubareva Source Type: research
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by th...
Source: Antiviral Research - September 17, 2023 Category: Virology Authors: Rongyuan Gao Philippe Noriel Q Pascua Ha T Nguyen Anton Chesnokov Chloe Champion Vasiliy P Mishin Dave E Wentworth Larisa V Gubareva Source Type: research
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by th...
Source: Antiviral Research - September 17, 2023 Category: Virology Authors: Rongyuan Gao Philippe Noriel Q Pascua Ha T Nguyen Anton Chesnokov Chloe Champion Vasiliy P Mishin Dave E Wentworth Larisa V Gubareva Source Type: research
Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022
Curr Med Chem. 2023 Sep 7. doi: 10.2174/0929867331666230907093501. Online ahead of print.ABSTRACTIn recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention ...
Source: Current Medicinal Chemistry - September 11, 2023 Category: Chemistry Authors: Roberto Romeo Laura Legnani Maria Assunta Chiacchio Salvatore V Giofr è Daniela Iannazzo Source Type: research
Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022
Curr Med Chem. 2023 Sep 7. doi: 10.2174/0929867331666230907093501. Online ahead of print.ABSTRACTIn recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention ...
Source: Current Medicinal Chemistry - September 11, 2023 Category: Chemistry Authors: Roberto Romeo Laura Legnani Maria Assunta Chiacchio Salvatore V Giofr è Daniela Iannazzo Source Type: research
Escherichia coli BL21(DE3) optimized deletion mutant as the host for whole-cell biotransformation of N ‑acetyl‑D‑neuraminic acid
In this study, via single-plasmid biotransformation system, we showed that the AGE gene BT0453, cloned from human gut microorganism Bacteroides thetaiotaomicron VPI-5482, showed the highest biotransformation yield among the AGE genes tested; and there is no clear Neu5Ac yield difference between the BT0453 coupled with one aldolase coding nanA gene and two nanA genes. Next, Escherichia coli chromosomal genes involved in substrate degradation, product exportation and pH change were deleted via recombineering and CRISPR/Cas9. With the final E. coli BL21(DE3) ΔnanA Δnag ΔpoxB as host, a significant 16.5% yield improvement w...
Source: Biotechnology Letters - September 9, 2023 Category: Biotechnology Authors: Qiong Zhang Jiao Zhang Yanhong Shao Guangdong Shang Source Type: research
Escherichia coli BL21(DE3) optimized deletion mutant as the host for whole-cell biotransformation of N ‑acetyl‑D‑neuraminic acid
In this study, via single-plasmid biotransformation system, we showed that the AGE gene BT0453, cloned from human gut microorganism Bacteroides thetaiotaomicron VPI-5482, showed the highest biotransformation yield among the AGE genes tested; and there is no clear Neu5Ac yield difference between the BT0453 coupled with one aldolase coding nanA gene and two nanA genes. Next, Escherichia coli chromosomal genes involved in substrate degradation, product exportation and pH change were deleted via recombineering and CRISPR/Cas9. With the final E. coli BL21(DE3) ΔnanA Δnag ΔpoxB as host, a significant 16.5% yield improvement w...
Source: Biotechnology Letters - September 9, 2023 Category: Biotechnology Authors: Qiong Zhang Jiao Zhang Yanhong Shao Guangdong Shang Source Type: research
Escherichia coli BL21(DE3) optimized deletion mutant as the host for whole-cell biotransformation of N ‑acetyl‑D‑neuraminic acid
In this study, via single-plasmid biotransformation system, we showed that the AGE gene BT0453, cloned from human gut microorganism Bacteroides thetaiotaomicron VPI-5482, showed the highest biotransformation yield among the AGE genes tested; and there is no clear Neu5Ac yield difference between the BT0453 coupled with one aldolase coding nanA gene and two nanA genes. Next, Escherichia coli chromosomal genes involved in substrate degradation, product exportation and pH change were deleted via recombineering and CRISPR/Cas9. With the final E. coli BL21(DE3) ΔnanA Δnag ΔpoxB as host, a significant 16.5% yield improvement w...
Source: Biotechnology Letters - September 9, 2023 Category: Biotechnology Authors: Qiong Zhang Jiao Zhang Yanhong Shao Guangdong Shang Source Type: research
