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10.1038/s41586-020-2601-5 http://scihub22266oqcxt.onion/10.1038/s41586-020-2601-5 32726803!7116779!32726803     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       Nature 2020 ; 587 (7835): 657-662 Nephropedia Template TP {{tp|p=32726803|t=2020. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity |pdf=|usr=}}{{32726803}} gab.com Text Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=32726803 #FOAvip The papain-like protease PLpro is an essential coronavirus enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread(1,2). PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an evasion mechanism against host antiviral immune responses(3-5). Here we perform biochemical, structural and functional characterization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro (SCoV2-PLpro) and outline differences with SARS-CoV PLpro (SCoV-PLpro) in regulation of host interferon and NF-kappaB pathways. SCoV2-PLpro and SCoV-PLpro share 83% sequence identity but exhibit different host substrate preferences; SCoV2-PLpro preferentially cleaves the ubiquitin-like interferon-stimulated gene 15 protein (ISG15), whereas SCoV-PLpro predominantly targets ubiquitin chains. The crystal structure of SCoV2-PLpro in complex with ISG15 reveals distinctive interactions with the amino-terminal ubiquitin-like domain of ISG15, highlighting the high affinity and specificity of these interactions. Furthermore, upon infection, SCoV2-PLpro contributes to the cleavage of ISG15 from interferon responsive factor 3 (IRF3) and attenuates type I interferon responses. Notably, inhibition of SCoV2-PLpro with GRL-0617 impairs the virus-induced cytopathogenic effect, maintains the antiviral interferon pathway and reduces viral replication in infected cells. These results highlight a potential dual therapeutic strategy in which targeting of SCoV2-PLpro can suppress SARS-CoV-2 infection and promote antiviral immunity. Twit Text FOAVip Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=32726803 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32726803 #FOAvip English Wikipedia <ref>{{Cite pmid|32726803}}</ref> Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity #MMPMID32726803 Shin D; Mukherjee R; Grewe D; Bojkova D; Baek K; Bhattacharya A; Schulz L; Widera M; Mehdipour AR; Tascher G; Geurink PP; Wilhelm A; van der Heden van Noort GJ; Ovaa H; Muller S; Knobeloch KP; Rajalingam K; Schulman BA; Cinatl J; Hummer G; Ciesek S; Dikic I Nature 2020[Nov]; 587 (7835): 657-662 PMID32726803show ga The papain-like protease PLpro is an essential coronavirus enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread(1,2). PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an evasion mechanism against host antiviral immune responses(3-5). Here we perform biochemical, structural and functional characterization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro (SCoV2-PLpro) and outline differences with SARS-CoV PLpro (SCoV-PLpro) in regulation of host interferon and NF-kappaB pathways. SCoV2-PLpro and SCoV-PLpro share 83% sequence identity but exhibit different host substrate preferences; SCoV2-PLpro preferentially cleaves the ubiquitin-like interferon-stimulated gene 15 protein (ISG15), whereas SCoV-PLpro predominantly targets ubiquitin chains. The crystal structure of SCoV2-PLpro in complex with ISG15 reveals distinctive interactions with the amino-terminal ubiquitin-like domain of ISG15, highlighting the high affinity and specificity of these interactions. Furthermore, upon infection, SCoV2-PLpro contributes to the cleavage of ISG15 from interferon responsive factor 3 (IRF3) and attenuates type I interferon responses. Notably, inhibition of SCoV2-PLpro with GRL-0617 impairs the virus-induced cytopathogenic effect, maintains the antiviral interferon pathway and reduces viral replication in infected cells. These results highlight a potential dual therapeutic strategy in which targeting of SCoV2-PLpro can suppress SARS-CoV-2 infection and promote antiviral immunity. |*Immunity, Innate[MESH] |Animals[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/*immunology/*virology[MESH] |Coronavirus Papain-Like Proteases/antagonists & inhibitors/*chemistry/*metabolism[MESH] |Cytokines/chemistry/metabolism[MESH] |Deubiquitinating Enzymes/antagonists & inhibitors/chemistry/metabolism[MESH] |Humans[MESH] |Interferon Regulatory Factor-3/metabolism[MESH] |Interferons/immunology/metabolism[MESH] |Mice[MESH] |Models, Molecular[MESH] |Molecular Dynamics Simulation[MESH] |NF-kappa B/immunology/metabolism[MESH] |Protein Binding[MESH] |SARS-CoV-2/drug effects/*enzymology/*immunology/physiology[MESH] |Ubiquitination[MESH]Papain-like protease regulates SARS-CoV-2 viral spread and innate immu(epmc).pdf DeepDyve Pubget Overpricing