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HGNC Genes

SARS-CoV-2 proteins

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    Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry MESHD

    Authors: Shiyou Zhu; Ying Liu; Zhuo Zhou; Zhiying Zhang; Xia Xiao; Zhiheng Liu; Ang Chen; Xiaojing Dong; Feng Tian; Shihua Chen; Yiyuan Xu; Chunhui Wang; Qiheng Li; Xuran Niu; Qian Pan; Shuo Du; Junyu Xiao; Jianwei Wang; Wensheng Wei

    doi:10.1101/2021.04.08.438924 Date: 2021-04-09 Source: bioRxiv

    The ongoing pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects MESHD a variety of tissues where the known receptor ACE2 HGNC is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection MESHD. In addition to known host proteins, i.e PROTEIN. ACE2 HGNC, TMPRSS2 HGNC, and NRP1 HGNC, we identified multiple host components, among which LDLRAD3 HGNC, TMEM30A HGNC, and CLEC4G HGNC were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain ( NTD HGNC). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 HGNC and CLEC4G HGNC mediate SARS-CoV-2 entry MESHD and infection in a fashion independent of ACE2 HGNC. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19 MESHD.

    SARS-CoV-2 Quasispecies Mediate Rapid Virus Evolution and Adaptation

    Authors: M. Zeeshan Chaudhry; Kathrin Eschke; Martina Grashoff; Leila Abassi; Yeonsu Kim; Linda Brunotte; Stephan Ludwig; Zeljka Macak Safranko; Ivan-Christian Kurolt; Alemka Markotic; Andrea Kroeger; Frank Klawonn; Luka Cicin-Sain

    doi:10.1101/2020.08.10.241414 Date: 2020-08-10 Source: bioRxiv

    The pandemic spread of SARS-CoV-2 and the resulting global healthcare emergency warrants a better understanding of its biology.The potential of SARS-CoV-2 evolution to create novel dangerous variants remain underexplored. Thus, we passaged SARS-CoV-2 in defined conditions and determined its genomic adaptation dynamics. We demonstrate the presence of remarkably stable SARS-CoV-2 quasispecies. We further show that the quasispecies nature of the virus population ensured rapid adaptation of the spike PRRARS motif upon passaging in Vero cells. On the other hand, SARS-CoV-2 replication in TMPRSS2 HGNC expressing cells led to a reverse mutation at the same site. We observed the emergence of novel mutations in envelope protein PROTEIN upon virus culture in Calu-3 and Caco-2 cells. Finally, we show that the heparan sulfate-binding motif (PRRARS) of the SARS-CoV-2 S protein PROTEIN acted as a determinant of negative growth selection. Overall, our research has far-reaching implications for development of antiviral strategies, suggesting viral quasispecies may facilitate rapid emergence of escape mutants under selection pressure, such as the treatment with antivirals against SARS-CoV-2.

    Unravelling the debate on heme effects in COVID-19 MESHD infections

    Authors: Marie-Therese Hopp; Daniel Domingo-Fernandez; Yojana Gadiya; Milena S Detzel; Benjamin F Schmalohr; Francel Steinbock; Diana Imhof; Martin Hofmann-Apitius

    doi:10.1101/2020.06.09.142125 Date: 2020-06-10 Source: bioRxiv

    The SARS-CoV-2 outbreak was recently declared a worldwide pandemic. Infection triggers the respiratory tract disease COVID-19 MESHD, which is accompanied by serious changes of clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis MESHD, which is characterized by an increase in labile heme. We present two approaches that aim at analyzing a potential link between available heme and COVID-19 MESHD pathogenesis. Four COVID-19 MESHD related proteins, i.e PROTEIN. the host cell proteins ACE2 HGNC and TMPRSS2 HGNC as well as the viral protein 7a and S protein PROTEIN, were identified as potential heme binders. We also performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 MESHD pathophysiology. Herein, focus was laid on inflammatory pathways, and distinct biomarkers as the linking elements. Finally, the results substantially improve our understanding of COVID-19 MESHD infections and disease progression of patients with different clinical backgrounds and expand the diagnostic and treatment options.

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MeSH Disease
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