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10.1038/s41419-021-03513-1 http://scihub22266oqcxt.onion/10.1038/s41419-021-03513-1 33762578!7987752!33762578     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Cell+Death+Dis 2021 ; 12 (4): 310 Nephropedia Template TP {{tp|p=33762578|t=2021. Inhibition of HECT E3 ligases as potential therapy for COVID-19 |pdf=|usr=}}{{33762578}} gab.com Text Inhibition of HECT E3 ligases as potential therapy for COVID-19 JO: Cell Death Dis http://www.kidney.de/pget.php?&tw=1&pmid=33762578 #FOAvip SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds. Twit Text FOAVip Inhibition of HECT E3 ligases as potential therapy for COVID-19 ????Cell Death Dis http://www.kidney.de/pget.php?&tw=1&pmid=33762578 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33762578 #FOAvip English Wikipedia <ref>{{Cite pmid|33762578}}</ref> Inhibition of HECT E3 ligases as potential therapy for COVID-19 #MMPMID33762578 Novelli G; Liu J; Biancolella M; Alonzi T; Novelli A; Patten JJ; Cocciadiferro D; Agolini E; Colona VL; Rizzacasa B; Giannini R; Bigio B; Goletti D; Capobianchi MR; Grelli S; Mann J; McKee TD; Cheng K; Amanat F; Krammer F; Guarracino A; Pepe G; Tomino C; Tandjaoui-Lambiotte Y; Uzunhan Y; Tubiana S; Ghosn J; Notarangelo LD; Su HC; Abel L; Cobat A; Elhanan G; Grzymski JJ; Latini A; Sidhu SS; Jain S; Davey RA; Casanova JL; Wei W; Pandolfi PP Cell Death Dis 2021[Mar]; 12 (4): 310 PMID33762578show ga SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds. |*COVID-19 Drug Treatment[MESH] |Adult[MESH] |Aged[MESH] |Animals[MESH] |Antiviral Agents/pharmacology[MESH] |COVID-19/*enzymology/genetics/metabolism[MESH] |Chlorocebus aethiops[MESH] |Endosomal Sorting Complexes Required for Transport/metabolism[MESH] |Female[MESH] |Humans[MESH] |Indoles/pharmacology[MESH] |Male[MESH] |Mice[MESH] |Mice, Inbred BALB C[MESH] |Middle Aged[MESH] |Nedd4 Ubiquitin Protein Ligases/genetics/metabolism[MESH] |SARS-CoV-2/isolation & purification/metabolism[MESH] |Spike Glycoprotein, Coronavirus/metabolism[MESH] |Ubiquitin-Protein Ligases/*antagonists & inhibitors/genetics/*metabolism[MESH] |Ubiquitination[MESH]Inhibition of HECT E3 ligases as potential therapy for COVID-19 (epmc).pdf DeepDyve Pubget Overpricing