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The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment (1H, 13C, 15N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.
Die Verlandungsvegetation des Dümmers wurde seit Beginn des 20. Jahrhunderts mehrfach untersucht. 2006 erfolgte erstmals eine flächendeckende Kartierung der gesamten Verlandungszone. Seit der 1953 abgeschlossenen Eindeichung war diese massiven Veränderungen unterworfen. Bereits kurz nach Deichschluss kam es zu einer massiven Reduktion der seeseitigen, durchfluteten Schilfbestände (Phragmites australis). Weite Röhrichtpartien entwickelten sich zunächst zu Wasserschwaden-Beständen (Glyceria maxima), dann wieder zu Schilfröhrichten. Nach einer zwischenzeitlichen Stagnation der Röhrichtabbrüche in den 1980er Jahren kam es in den letzten 15-20 Jahren zu erneuten erheblichen Flächenverlusten. Die ehemals typischen Teichbinseninseln (Schoenoplectus spp.) sind inzwischen weitestgehend verschwunden. Die Wasserrosenfelder (Nuphar lutea, Nymphaea alba) verloren seit den 1990er Jahren erheblich an Fläche. Alle Verluste an der Verlandungsvegetation dürften zunächst durch die Gewässerbelastung, in neuerer Zeit vor allem durch zu hoch gehaltene Sommerwasserstände verursacht sein. Die ehemals üppige und artenreiche submerse Vegetation starb nach der Eindeichung vollständig ab. Nach einer unerwartet eingetretenen Klarwasserphase wurde 2001 erstmals wieder Potamogeton pectinatus nachgewiesen, seitdem wurden weitere Laichkraut-Arten, zwei Arten der Armleuchteralgen (Chara fragilis, Nitella mucronata) und weitere Tauch- und Schwimmblattpflanzen nachgewiesen. Die voraussichtlich 2009 erfolgende Umleitung des Bornbaches, über den ein Großteil der heutigen Nährstofffracht in den Dümmer gelangt, dürfte die Bedingungen für die submerse Vegetation entscheidend verbessern.
The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Using a data sample of e+e− collision data corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at a center-of-mass energy of s=3.773GeV, we search for the singly Cabibbo-suppressed decays D0→π0π0π0, π0π0η, π0ηη and ηηη using the double tag method. The absolute branching fractions are measured to be B(D0→π0π0π0)=(2.0±0.4±0.3)×10−4, B(D0→π0π0η)=(3.8±1.1±0.7)×10−4 and B(D0→π0ηη)=(7.3±1.6±1.5)×10−4 with the statistical significances of 4.8σ, 3.8σ and 5.5σ, respectively, where the first uncertainties are statistical and the second ones systematic. No significant signal of D0→ηηη is found, and the upper limit on its decay branching fraction is set to be B(D0→ηηη)<1.3×10−4 at the 90% confidence level.