About: Targeting heparan sulfate proteoglycan-assisted endocytosis as a COVID-19 therapeutic option

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About: Targeting heparan sulfate proteoglycan-assisted endocytosis as a COVID-19 therapeutic option Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Targeting heparan sulfate proteoglycan-assisted endocytosis as a COVID-19 therapeutic option
Creator	Zhang, Qi Zheng, Wei Xu, Yue Huang, Wenwei Xu, Miao Ye, Yihong Chen, Catherine Shen, Min Lee, Juhyung Luo, Zhiji Pradhan, Manisha Swaroop, Manju Wang, Lihui
Source	BioRxiv; Medline
abstract	Drugs capable of blocking the infectious cycle of the coronavirus SARS-CoV-2 are urgently needed to tackle the ongoing COVID-19 pandemic. To this end, the cell entry of SARS-CoV-2, initiated by the binding of the viral Spike (S) protein to human ACE2, has emerged as an attractive drug repurposing target. Here we use murine leukemia viruses pseudotyped with Spike from SARS-CoV or SARS-CoV-2 to demonstrate that ACE2-mediated coronavirus entry can be mitigated by heparin, a heparan sulfate-related glycan, or by genetic ablation of biosynthetic enzymes for the cell surface heparan sulfate proteoglycans (HSPGs). A drug repurposing screen targeting HSPG-dependent endocytosis identifies pharmacologically active endocytosis inhibitors that also abrogate coronavirus cell entry. Among them, Mitoxantrone (EC50=~10 nM) targets HSPGs directly, whereas Sunitinib and BNTX disrupt the actin network to impair HSPG-assisted viral entry. Gene expression profiling suggests potential combination regimens that optimally target HSPG-dependent viral entry. Altogether, our study establishes HSPGs as an assisting factor for ACE2 in endocytosis-mediated coronavirus entry and identifies drugs that can be repurposed to target this important stage in the viral life cycle.
has issue date	2020-07-14(xsd:dateTime)
bibo:doi	10.1101/2020.07.14.202549
bibo:pmid	32699847
has license	biorxiv
sha1sum (hex)	1d5f2686596949379b07871483c508a755f630a5
schema:url	https://doi.org/10.1101/2020.07.14.202549
resource representing a document's title	Targeting heparan sulfate proteoglycan-assisted endocytosis as a COVID-19 therapeutic option
has PubMed identifier	32699847
schema:publication	bioRxiv
resource representing a document's body	covid:1d5f2686596949379b07871483c508a755f630a5#body_text
is schema:about of	named entity 'drug repurposing' named entity 'target' named entity 'biosynthetic' named entity 'therapeutic' covid:arg/1d5f2686596949379b07871483c508a755f630a5 named entity 'viruses' named entity 'inhibitors' named entity 'proteoglycans' named entity 'mitigated' named entity 'endocytosis' named entity 'ACE2' named entity 'heparan sulfate proteoglycans' named entity 'protein' named entity 'pseudotyped' named entity 'HSPG' named entity 'initiated' named entity 'heparan sulfate' named entity 'Sunitinib' named entity 'antiviral agent' named entity 'monomers' named entity 'ACE2' named entity 'HSPG' named entity 'interferon' named entity 'lymphocytic leukemia' named entity 'ACE2' named entity 'actin' named entity 'gene expression' named entity 'HSPG' named entity 'cell growth' named entity 'epithelial cells' named entity 'MLV' named entity 'cell lines' named entity 'sulfation' named entity 'Mitoxantrone' named entity 'ligands' named entity 'PerkinElmer' named entity 'cell membranes' named entity 'protein families' named entity 'conformational change' named entity 'Magnesium Chloride' named entity 'gene silencing' named entity 'qPCR' named entity 'SARS-CoV-2' named entity 'HEK293T' named entity 'differential centrifugation' named entity 'actin filaments' named entity 'Glypicans' named entity 'HSPG' named entity 'fibril' named entity 'chain initiation' named entity 'EGFP' named entity 'basal membranes' named entity 'cell metabolism' named entity 'HSPGs' named entity 'Spike protein' named entity 'DMSO' named entity 'anti-cancer' named entity 'SLC35B2' named entity 'host cells' named entity 'retrovirus' named entity 'polycation' named entity 'gene expression' named entity 'subcellular fractionation' named entity 'phosphate' named entity 'endocytic' named entity 'Calu-3' named entity 'S100' named entity 'endocytosis' named entity 'Heparin' named entity 'ACE2'

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