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

Atmospheric and Surface Processes, and Feedback Mechanisms Determining Arctic Amplification: A Review of First Results and Prospects of the (AC)3 Project

Mechanisms behind the phenomenon of Arctic amplification are widely discussed. To contribute to this debate, the (AC)3 project has been established in 2016. It comprises modeling and data analysis efforts as well as observational elements. The project has assembled a wealth of ground-based, airborne, ship-borne, and satellite data of physical, chemical, and meteorological properties of the Arctic atmosphere, cryosphere, and upper ocean that are available for the Arctic climate research community. Short-term changes and indications of long-term trends in Arctic climate parameters have been detected using existing and new data

How well do state-of-the-art Atmosphere-Ocean general circulation models reproduce atmospheric teleconnection patterns?

This article evaluates the ability of state-of-the-art climate models to reproduce the low-frequency variability of the mid-tropospheric winter flow of the Northern Hemisphere in terms of atmospheric teleconnection patterns. Therefore, multi-model simulations for present-day conditions, performed for the 4th assessment report of the Intergovernmental Panel on Climate Change, have been analysed and compared with re-analysis data sets. The spatial patterns of atmospheric teleconnections are reproduced reasonably by most of the models. The comparison of coupled with atmosphere-only runs confirmed that a better representation of the forcing by sea surface temperatures has the potential to slightly improve the representation of only wave train-like patterns. Due to internally generated climate variability, the models are not able to reproduce the observed temporal behaviour. Insights into the dynamical reasons for the limited skill of climate models in reproducing teleconnections have been obtained by studying the relation between major teleconnections and zonal wind variability patterns. About half of the models are able to reproduce the observed relationship. For these cases, the quality of simulated teleconnection patterns is largely determined by the quality of zonal wind variability patterns. Therefore, improvements of simulated eddy-mean flow interaction have the potential to improve the atmospheric teleconnections

Springtime Arctic aerosol: Smoke versus Haze, a case study for March 2008

During March 2008 photometer observations of Arctic aerosol were performed both at a Russian ice-floe drifting station (NP-35) at the central Arctic ocean (56.7e42.0 E, 85.5e84.2 N) and at Ny-Ålesund, Spitsbergen (78.9 N, 11.9 E). Next to a persistent increase of AOD over NP-35, two pronounced aerosol events have been recorded there, one originating from early season forest fires close to the city of Khabarovsk (“Arctic Smoke”), the other one showed trajectories from central Russia and resembled more the classical Arctic Haze. The latter event has also been recorded two days later over Ny-Ålesund, both in photometer and lidar. From these remote sensing instruments volume distribution functions are derived and discussed. Only subtle differences between the smoke and the haze event have been found in terms of particle microphysics. Different trajectory analysis, driven by NCEP and ECMWF have been performed and compared. For the data set presented here the meteorological field, due to sparseness of data in the central Arctic, mainly limits the precision of the air trajectories