SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals

Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC(50) values of 136.7, 7.67, 0.11, and 0.13 μM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19

Erarbeitung rollstuhltechnologischer Kenndaten fuer die Weiterentwicklung und Verbesserung der Ueberwachung, Steuerung und Regelung des Systems 'Batteriegetriebener 2-Motoren-Rollstuhl (mittels Mikrocomputer)' sowie Pilotanwendung dieser Steuerung Abschlussbericht

With 2 refs., 1 tab., 25 figs.Copy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Aakkiartorpoq!: Frozen-Ground Cartoons; Eqqumiitsuliortut nunalu qeriuaannartoq pillugu ilisimatuut akornanni suleqatigiinneq

This project started in October 2015 with a crazy idea: prepare and submit a funding application for an international, multidisciplinary and non-traditional scientific outreach project… within the next 48 hours. Well, it worked out. A group of highly motivated young researchers from Canada and Europe united to combine arts and science and produce a series of outreach comic strips about permafrost (frozen ground). The aim of the project is to present and explain scientific research conducted across the circumpolar Arctic, placing emphasis on field work and the rapidly changing northern environment. The target audience is kids, youth, parents and teachers, with the general goal of making permafrost science more fun and accessible to the public. Because guess what : permafrost represents an area of more than twenty million km2 in the Northern Hemisphere, a huge area. As the climate warms, permafrost thaws and becomes unstable for houses, roads and airports. This rapid thawing of previously frozen ground also disrupts plant and animal habitats, impacts water quality and the ecology of lakes, and releases carbon into the atmosphere as greenhouse gases, making climate change even stronger. Hence permafrost and its response to climate change concerns us all. The project received initial support from the International Permafrost Association (IPA) as a targeted ‘Action Group’, and since then several other sponsors have joined the project. Here we are, now, two years after this first idea. What you are about to read is the result of an iterative process of exchanging ideas between artists and scientists. We first made an application call and received 49 applications from artists in 16 countries. Through a formal review process, we then selected two artists to work on this project: Noémie Ross from Canada, and Heta Nääs from Finland. With input from scientists, Noémie and Heta created fantastic cartoons that explain some of the changes happening to the environment in permafrost areas, how they affect people and wildlife, and what scientists are doing to better understand these changes to help people find innovative ways to adapt. We wish everyone plenty of fun reading this booklet and we would like to thank all those who supported this project