Processing of the SARS-CoV pp1a/ab nsp7-10 region.
TLDR
In this paper, the authors analyzed processing of the coronavirus nsp7-10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation.Abstract:
Severe acute respiratory syndrome coronavirus is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/transcription complex, essential steps include processing of the conserved polyprotein nsp7-10 region by the main protease Mpro and subsequent complex formation of the released nsp's. Here, we analyzed processing of the coronavirus nsp7-10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2 : 2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.read more
Citations
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Yosra A. Helmy,Yosra A. Helmy,Mohamed Fawzy,Ahmed Elaswad,Ahmed Sobieh,Scott P. Kenney,Awad A. Shehata +6 more
TL;DR: A pneumonia outbreak with unknown etiology was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market, producing the disease named coronavirus disease-2019 (COVID-19), which the WHO has declared a pandemic.
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Malihe Mohamadian,Hossein Chiti,Alireza Shoghli,Sajjad Biglari,Negin Parsamanesh,Abdolreza Esmaeilzadeh +5 more
TL;DR: At the end of December 2019, a novel coronavirus tentatively named SARS‐CoV‐2 in Wuhan, a central city in China, was announced by the World Health Organization.
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The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells
Jan Wenzel,Josephine Lampe,Helge Müller-Fielitz,Raphael Schuster,Marietta Zille,Kristin Müller,Markus Krohn,Jakob Körbelin,Linlin Zhang,Umit Ozorhan,Vanessa Neve,Julian U. G. Wagner,Denisa Bojkova,Mariana Shumliakivska,Yun Jiang,Anke Fähnrich,Fabian Ott,Valentin Sencio,Cyril Robil,Susanne Pfefferle,Florent Sauve,Caio Coelho,Jonas Franz,Jonas Franz,Frauke Spiecker,Beate Lembrich,Sonja Binder,Nina Feller,Peter König,Hauke Busch,Ludovic Collin,Roberto Villaseñor,Olaf Jöhren,Hermann C. Altmeppen,Manolis Pasparakis,Stefanie Dimmeler,Jindrich Cinatl,Klaus Püschel,Matija Zelic,Dimitry Ofengeim,Christine Stadelmann,François Trottein,Rubén Nogueiras,Rolf Hilgenfeld,Markus Glatzel,Vincent Prevot,Markus Schwaninger +46 more
TL;DR: In this article, structural changes in cerebral small vessels of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models were investigated.
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SARS-CoV-2 infection, COVID-19 pathogenesis, and exposure to air pollution: What is the connection?
TL;DR: Air pollution exposure may affect different stages of the viral life cycle, including inhibition of mucociliary clearance, alteration of viral receptors and proteases required for entry, changes to antiviral interferon production and viral replication, changes in viral assembly mediated by autophagy, prevention of uptake by macrophages, and promotion of viral spread by increasing epithelial permeability.
Posted ContentDOI
The SARS-CoV-2 main protease M-pro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells
Jan Wenzel,J. Lampe,H. Mueler-Fielitz,K. Mueler,R. Schuster,M. Zille,L. Zhang,M. Krohn,V. Neve,H. Altmeppen,F. Sauve,M. Pasparakis,V. Prevot,R. Hilgenfeld,M. Glatzel,Markus Schwaninger +15 more
TL;DR: The inhibition of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood-brain barrier due to NEMO ablation, suggesting RIPK as a therapeutic target to treat the neuropathology of COVID-19.
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TL;DR: This series of crystal structures, which is the first, to the authors' knowledge, of any protein from the SARS virus, reveal substantial pH-dependent conformational changes, and an unexpected mode of inhibitor binding, providing a structural basis for rational drug design.
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