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10.7554/eLife.69719 http://scihub22266oqcxt.onion/10.7554/eLife.69719 34402426!8457835!34402426     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 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Elife 2021 ; 10 (ä): ä Nephropedia Template TP {{tp|p=34402426|t=2021. A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance |pdf=|usr=}}{{34402426}} gab.com Text A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance JO: Elife http://www.kidney.de/pget.php?&tw=1&pmid=34402426 #FOAvip BACKGROUND: The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19. METHODS: To identify host proteins that may contribute to the risk of severe COVID-19, we undertook proteome-wide genetic colocalisation tests, and polygenic (pan) and cis-Mendelian randomisation analyses leveraging publicly available protein and COVID-19 datasets. RESULTS: Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble Fas (colocalisation probability >0.9, p=1 x 10(-4)), implicating Fas-mediated apoptosis as a potential target for COVID-19 risk. The polygenic (pan) and cis-Mendelian randomisation analyses showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal is highly pleiotropic, and a look-up of proteins associated with the ABO signal revealed that the strongest association was with soluble CD209. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19. CONCLUSIONS: Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19. FUNDING: MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/4). JSh and GJW were funded by the Wellcome Trust Grant 206194. This research was funded in part by the Wellcome Trust [Grant 206194]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Twit Text FOAVip A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance ????Elife http://www.kidney.de/pget.php?&tw=1&pmid=34402426 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34402426 #FOAvip English Wikipedia <ref>{{Cite pmid|34402426}}</ref> A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance #MMPMID34402426 Anisul M; Shilts J; Schwartzentruber J; Hayhurst J; Buniello A; Shaikho Elhaj Mohammed E; Zheng J; Holmes M; Ochoa D; Carmona M; Maranville J; Gaunt TR; Emilsson V; Gudnason V; McDonagh EM; Wright GJ; Ghoussaini M; Dunham I Elife 2021[Aug]; 10 (ä): ä PMID34402426show ga BACKGROUND: The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19. METHODS: To identify host proteins that may contribute to the risk of severe COVID-19, we undertook proteome-wide genetic colocalisation tests, and polygenic (pan) and cis-Mendelian randomisation analyses leveraging publicly available protein and COVID-19 datasets. RESULTS: Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble Fas (colocalisation probability >0.9, p=1 x 10(-4)), implicating Fas-mediated apoptosis as a potential target for COVID-19 risk. The polygenic (pan) and cis-Mendelian randomisation analyses showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal is highly pleiotropic, and a look-up of proteins associated with the ABO signal revealed that the strongest association was with soluble CD209. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19. CONCLUSIONS: Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19. FUNDING: MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/4). JSh and GJW were funded by the Wellcome Trust Grant 206194. This research was funded in part by the Wellcome Trust [Grant 206194]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. |*Genome-Wide Association Study[MESH] |2',5'-Oligoadenylate Synthetase/genetics[MESH] |COVID-19/genetics/immunology/physiopathology/*virology[MESH] |Cell Adhesion Molecules[MESH] |Humans[MESH] |Lectins, C-Type[MESH] |Proteome[MESH] |Receptors, Cell Surface[MESH] |SARS-CoV-2/*physiology[MESH] |Scavenger Receptors, Class A/genetics[MESH] |Severity of Illness Index[MESH]A proteome-wide genetic investigation identifies several SARS-CoV-2-ex(epmc).pdf DeepDyve Pubget Overpricing