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      Cryo-EM structure of coronavirus-HKU1 haemagglutinin esterase reveals architectural changes arising from prolonged circulation in humans

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          Abstract

          The human betacoronaviruses HKU1 and OC43 (subgenus Embecovirus) arose from separate zoonotic introductions, OC43 relatively recently and HKU1 apparently much longer ago. Embecovirus particles contain two surface projections called spike (S) and haemagglutinin-esterase (HE), with S mediating receptor binding and membrane fusion, and HE acting as a receptor-destroying enzyme. Together, they promote dynamic virion attachment to glycan-based receptors, specifically 9- O-acetylated sialic acid. Here we present the cryo-EM structure of the ~80 kDa, heavily glycosylated HKU1 HE at 3.4 Å resolution. Comparison with existing HE structures reveals a drastically truncated lectin domain, incompatible with sialic acid binding, but with the structure and function of the esterase domain left intact. Cryo-EM and mass spectrometry analysis reveals a putative glycan shield on the now redundant lectin domain. The findings further our insight into the evolution and host adaptation of human embecoviruses, and demonstrate the utility of cryo-EM for studying small, heavily glycosylated proteins.

          Abstract

          Human coronavirus-HKU1 contains two surface projections called spike and haemagglutinin-esterase (HE), with the latter acting as a receptor-destroying enzyme. Here, the authors use cryo-EM and mass spectrometry to characterise the small, heavily glycosylated HKU1 HE, revealing a vestigial lectin domain covered with a putative glycan shield; and they discuss these features in the context of host adaptation.

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

            A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
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              Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

              The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Contributors
                d.l.hurdiss@uu.nl
                r.j.degroot@uu.nl
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                16 September 2020
                16 September 2020
                2020
                : 11
                Affiliations
                [1 ]GRID grid.5477.1, ISNI 0000000120346234, Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, , Utrecht University, ; Yalelaan 1, 3584 CH Utrecht, The Netherlands
                [2 ]GRID grid.5477.1, ISNI 0000000120346234, Cryo-Electron Microscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, , Utrecht University, ; Padualaan 8, 3584 CH Utrecht, The Netherlands
                [3 ]GRID grid.433187.a, Materials and Structural Analysis, , Thermo Fisher Scientific, ; Achtseweg Noord 5, Eindhoven, 5651 GG The Netherlands
                [4 ]GRID grid.5477.1, ISNI 0000000120346234, Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, , Utrecht University, ; Padualaan 8, 3584 CH Utrecht, The Netherlands
                Article
                18440
                10.1038/s41467-020-18440-6
                7495468
                32938911
                c08d7167-cf9b-4bec-b62c-c333e03325ef
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                Funding
                Funded by: China Scholarship Council grant (No 2014-03250042).
                Funded by: Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI, 024.002.009).
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                viral evolution,virus structures,cryoelectron microscopy
                Uncategorized
                viral evolution, virus structures, cryoelectron microscopy

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