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Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics
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Academic Article
research paper
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Covid-on-the-Web dataset
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
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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.
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2020-04-15
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10.1101/2020.04.15.997254
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biorxiv
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fa85d1b316bb19d302f89e2a0404597de4d973db
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https://doi.org/10.1101/2020.04.15.997254
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Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics
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bioRxiv
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covid:fa85d1b316bb19d302f89e2a0404597de4d973db#body_text
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named entity 'vaccines'
covid:arg/fa85d1b316bb19d302f89e2a0404597de4d973db
named entity 'Diseases'
named entity 'Medical Parasitology'
named entity 'MK-2206'
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