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SARS-CoV-2 proteins

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    Interaction network of SARS-CoV-2 with host receptome through spike protein PROTEIN

    Authors: Yunqing Gu; Jun Cao; Xinyu Zhang; Hai Gao; Yuyan Wang; Jia Wang; Jinlan Zhang; Guanghui Shen; Xiaoyi Jiang; Jie Yang; Xichen Zheng; Jianqing Xu; Cheng Cheng Zhang; Fei Lan; Di Qu; Yun Zhao; Guoliang Xu; Youhua Xie; Min Luo; Zhigang Lu; Khatendra Reang; Akadiri Olalekan; Sarah H Carl; Ali Doga Yucel; Ozgur Can; Serena Ozabrahamyan; Alpsu Olkan; Ece Erdemoglu; Fulya Aksit; Gokhan Haci Tanisali; Oleksandr M. Yefanov; Anton Barty; Alexandra Tolstikova; Gihan K. Ketawala; Sabine Botha; E. Han Dao; Brandon Hayes; Mengning Liang; Matthew H Seaberg; Mark S. Hunter; Alex Batyuk; Valerio Mariani; Zhen Su; Frederic Poitevin; Chun Hong Yoon; Christopher J. Kupitz; Raymond G. Sierra; Edward H Snell; Hasan DeMirci

    doi:10.1101/2020.09.09.287508 Date: 2020-09-09 Source: bioRxiv

    Host cellular receptors are key determinants of virus tropism MESHD and pathogenesis. Virus utilizes multiple receptors for attachment, entry, or specific host responses. However, other than ACE2 HGNC, little is known about SARS-CoV-2 receptors. Furthermore, ACE2 HGNC cannot easily interpret the multi-organ tropisms of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV MESHD. To identify host cell receptors involved in SARS-CoV-2 interactions, we performed genomic receptor profiling to screen almost all human membrane proteins, with SARS-CoV-2 capsid spike (S) protein PROTEIN as the target. Twelve receptors were identified, including ACE2 HGNC. Most receptors bind at least two domains on S protein PROTEIN, the receptor-binding-domain (RBD) and the N-terminal-domain ( NTD HGNC), suggesting both are critical for virus-host interaction. Ectopic expression of ASGR1 HGNC or KREMEN1 HGNC is sufficient to enable entry of SARS-CoV-2, but not SARS-CoV MESHD and MERS-CoV. Analyzing single-cell transcriptome profiles from COVID-19 MESHD patients revealed that virus susceptibility in airway epithelial ciliated and secretory cells and immune macrophages highly correlates with expression of ACE2 HGNC, KREMEN1 HGNC and ASGR1 HGNC respectively, and ACE2 HGNC/ ASGR1 HGNC/ KREMEN1 HGNC (ASK) together displayed a much better correlation than any individual receptor. Based on modeling of systemic SARS-CoV-2 host interactions through S receptors, we revealed ASK correlation with SARS-CoV-2 multi-organ tropism MESHD and provided potential explanations for various COVID-19 MESHD symptoms. Our study identified a panel of SARS-CoV-2 receptors with diverse binding properties, biological functions, and clinical correlations or implications, including ASGR1 HGNC and KREMEN1 HGNC as the alternative entry receptors, providing insights into critical interactions of SARS-CoV-2 with host, as well as a useful resource and potential drug targets for COVID-19 MESHD investigation.

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MeSH Disease
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