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10.1073/pnas.2122897119 http://scihub22266oqcxt.onion/10.1073/pnas.2122897119 35700355!9245715!35700355     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2022 ; 119 (26): e2122897119 Nephropedia Template TP {{tp|p=35700355|t=2022. SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis |pdf=|usr=}}{{35700355}} gab.com Text SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=35700355 #FOAvip Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-kappaB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes. Twit Text FOAVip SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=35700355 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=35700355 #FOAvip English Wikipedia <ref>{{Cite pmid|35700355}}</ref> SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis #MMPMID35700355 Qin C; Rao Y; Yuan H; Wang TY; Zhao J; Espinosa B; Liu Y; Zhang S; Savas AC; Liu Q; Zarinfar M; Rice S; Henley J; Comai L; Graham NA; Chen C; Zhang C; Feng P Proc Natl Acad Sci U S A 2022[Jun]; 119 (26): e2122897119 PMID35700355show ga Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-kappaB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes. |*Antiviral Agents/pharmacology/therapeutic use[MESH] |*Aspartate Carbamoyltransferase/antagonists & inhibitors[MESH] |*COVID-19 Drug Treatment[MESH] |*Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)/antagonists & inhibitors[MESH] |*Dihydroorotase/antagonists & inhibitors[MESH] |*Enzyme Inhibitors/pharmacology/therapeutic use[MESH] |*Pyrimidines/antagonists & inhibitors/biosynthesis[MESH] |*SARS-CoV-2/drug effects/physiology[MESH] |*Virus Replication/drug effects[MESH] |Animals[MESH] |Enzyme Activation/drug effects[MESH] |Humans[MESH] |Inflammation/drug therapy[MESH] |Mice[MESH] |RNA-Binding Proteins/metabolism[MESH] |Transcription Factor RelA/metabolism[MESH]SARS-CoV-2 couples evasion of inflammatory response to activated nucle(epmc).pdf DeepDyve Pubget Overpricing