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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    SARS-CoV-2 comprehensive receptor profiling: mechanistic insight to drive new therapeutic strategies

    Authors: Sarah MV Brockbank; Raquel Faba-Rodriguez; Lyn Rosenbrier Ribeiro; Catherine Geh; Helen Thomas; Jenni Delight; Lucy Coverley; W Mark Abbott; Jo Soden; Jim Freeth

    doi:10.1101/2021.03.11.434937 Date: 2021-03-11 Source: bioRxiv

    Here we describe a hypothesis free approach to screen for interactions of SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN with human cell surface receptors. We used a library screening approach to detect binding interactions across one of the largest known panels of membrane-bound and soluble receptors, comprising 5845 targets, expressed recombinantly in human cells. We were able confirm and replicate SARS-CoV-2 binding to ACE2 HGNC and other putative coreceptors such as CD209 HGNC and CLEC4M HGNC. More significantly, we identified interactions with a number of novel SARS-CoV-2 S binding proteins. Three of these novel receptors, NID1 HGNC, CNTN1 HGNC and APOA4 HGNC were specific to SARS-CoV-2, and not SARS-COV MESHD, with APOA4 HGNC binding the S-protein HGNC S-protein PROTEIN with equal affinity as ACE2 HGNC. With this knowledge we may further understand the disease pathogenesis of COVID-19 MESHD patients and how infection by SARS-CoV-2 may lead to differences in pathology in specific organs or indeed the virulence observed in different ethnicities. Importantly we illustrate a methodology which can be used for rapid, unbiassed identification of cell surface receptors, to support drug screening and drug repurposing approaches for this and future pandemics.

    Proteomic Profiling in Biracial Cohorts Implicates DC-SIGN HGNC as a Mediator of Genetic Risk in COVID-19 MESHD

    Authors: Daniel H. Katz; Usman A. Tahir; Debby Ngo; Mark D. Benson; Alexander G. Bick; Akhil Pampana; Yan Gao; Michelle J. Keyes; Adolfo Correa; Sumita Sinha; Dongxiao Shen; Qiong Yang; Jeremy M. Robbins; Zsu-Zsu Chen; Daniel E. Cruz; Bennet Peterson; Pradeep Natarajan; Ramachandran S. Vasan; Gustav Smith; Thomas J. Wang; Robert E. Gerszten

    doi:10.1101/2020.06.09.20125690 Date: 2020-06-11 Source: medRxiv

    COVID-19 MESHD is one of the most consequential pandemics in the last century, yet the biological mechanisms that confer disease risk are incompletely understood. Further, heterogeneity in disease outcomes is influenced by race, though the relative contributions of structural/social and genetic factors remain unclear. Very recent unpublished work has identified two genetic risk loci that confer greater risk for respiratory failure MESHD in COVID-19 MESHD: the ABO HGNC locus and the 3p21.31 locus. To understand how these loci might confer risk and whether this differs by race, we utilized proteomic profiling and genetic information from three cohorts including black and white participants to identify proteins influenced by these loci. We observed that variants in the ABO HGNC locus are associated with levels of CD209 HGNC/ DC-SIGN HGNC, a known binding protein for SARS-CoV MESHD and other viruses, as well as multiple inflammatory and thrombotic proteins, while the 3p21.31 locus is associated with levels of CXCL16 HGNC, a known inflammatory chemokine. Thus, integration of genetic information and proteomic profiling in biracial cohorts highlights putative mechanisms for genetic risk in COVID-19 MESHD disease.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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