About: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics

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About: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics
Creator	Drosten, Christian Niemeyer, Daniela Papies, Jan Müller, Marcel Corman, M Gassen, Nils Richter, Anja Bajaj, Thomas Dethloff, Frederik Emanuel, Jackson Giavalisco, Patrick Heinemann, Nicolas Heinz, Daniel Lennarz, Martina Sechenov, Weckmann, Katja
Source	BioRxiv
abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an acute threat to public health and the world economy, especially because no approved specific drugs or vaccines are available. Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. Here we show that SARS-CoV-2 infection limits autophagy by interfering with multiple metabolic pathways and that compound-driven interventions aimed at autophagy induction reduce SARS-CoV-2 propagation in vitro. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Infection also downregulates autophagy-inducing spermidine, and facilitates AKT1/SKP2-dependent degradation of autophagy-initiating Beclin-1 (BECN1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In sum, SARS-CoV-2 infection causally diminishes autophagy. A clinically approved and well-tolerated autophagy-inducing compound shows potential for evaluation as a treatment against SARS-CoV-2.
has issue date	2020-04-15(xsd:dateTime)
bibo:doi	10.1101/2020.04.15.997254
has license	biorxiv
sha1sum (hex)	fa85d1b316bb19d302f89e2a0404597de4d973db
schema:url	https://doi.org/10.1101/2020.04.15.997254
resource representing a document's title	Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics
schema:publication	bioRxiv
resource representing a document's body	covid:fa85d1b316bb19d302f89e2a0404597de4d973db#body_text
is schema:about of	named entity 'vaccines' covid:arg/fa85d1b316bb19d302f89e2a0404597de4d973db named entity 'Diseases' named entity 'Medical Parasitology' named entity 'MK-2206' named entity 'antiviral' named entity 'AKT1' named entity 'mTORC1' named entity 'AKT1' named entity 'BECN1' named entity 'amino acids' named entity 'proteasomal degradation' named entity 'lysosomes' named entity 'virus' named entity 'LC3B' named entity 'metabolism' named entity 'cytosolic' named entity 'virus' named entity 'valinomycin' named entity 'red fluorescent protein' named entity 'SARS-CoV-2' named entity 'microtubule-associated protein' named entity 'monomers' named entity 'MERS' named entity 't-test' named entity 'BECN1' named entity 'mTORC1' named entity 'niclosamide' named entity 'fluorescence microscopy' named entity 'hydrogen' named entity 'SKP2' named entity 'antiviral' named entity 'SARS-CoV-2' named entity 'SARS-CoV-2' named entity 'LC3B' named entity 'niclosamide' named entity 'metabolism' named entity 'intracellular' named entity 'SARS-CoV-2' named entity 'life cycle' named entity 'SARS-CoV-2' named entity 'world economy' named entity 'light chain' named entity 'long-lived' named entity 'autophagy' named entity 'S-phase kinase-associated protein 2' named entity 'lipids' named entity 'valinomycin' named entity 'monomeric' named entity 'lipidated' named entity 'fluorescence' named entity 'Beclin-1' named entity 'spermidine' named entity 'virus' named entity 'autophagosomes' named entity 'substrates' named entity 'WORLD' named entity 'ECONOMY' named entity 'LC3B' named entity 'vaccines' named entity 'macromolecules' named entity 'EGFP' named entity 'green fluorescent protein' named entity 'AKT1' named entity 'public health' named entity 'BECN1' named entity 'eukaryotic cells' named entity 'endosomal' named entity 'niclosamide'

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