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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/1965| Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics | |
| Nils C Gassen. Jan Papies. Thomas Bajaj. Frederik Dethloff. Jackson Emanuel. Katja Weckmann. Daniel E. Heinz. Nicolas Heinemann. Martina Lennarz. Anja Richter. Daniela Niemeyer. Victor M Corman. Patrick Giavalisco. Christian Drosten. Marcel A Muller. | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.1101/2020.04.15.997254 | |
| 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. | |
| www.biorxiv.org | |
| 2020 | |
| Artículo | |
| https://www.biorxiv.org/content/10.1101/2020.04.15.997254v1.full.pdf | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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| 1100676.pdf | 2.64 MB | Adobe PDF | Visualizar/Abrir |