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      Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

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      1 , 2 , 3 , 1 , 2 , 1 , 2 , 4 , 5 , 6 , 7 , 4 , 3 , 1 , 2 , 8 , 3 , 9 , 7 , 7 , 7 , 10 , 11 , 12 , 13 , 13 , 3 , 9 , 14 , 15 , 16 , 17 , 8 , 3 , 19 , 20 , 5 , 21 , 7 , 11 , 22 , 4 , 3 , 18 , , 1 , 2 , 23 ,
      Science (New York, N.y.)
      American Association for the Advancement of Science

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Another host factor for SARS-CoV-2

          Virus-host interactions determine cellular entry and spreading in tissues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the earlier SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as a receptor; however, their tissue tropism differs, raising the possibility that additional host factors are involved. The spike protein of SARS-CoV-2 contains a cleavage site for the protease furin that is absent from SARS-CoV (see the Perspective by Kielian). Cantuti-Castelvetri et al. now show that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial and epithelial cells. Daly et al. found that the furin-cleaved S1 fragment of the spike protein binds directly to cell surface NRP1 and blocking this interaction with a small-molecule inhibitor or monoclonal antibodies reduced viral infection in cell culture. Understanding the role of NRP1 in SARS-CoV-2 infection may suggest potential targets for future antiviral therapeutics.

          Science, this issue p. 856, p. [Related article:]861; see also p. [Related article:]765

          Abstract

          NRP1 serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.

          Abstract

          The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.

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          Most cited references37

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            The Sequence Alignment/Map format and SAMtools

            Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk
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              A Novel Coronavirus from Patients with Pneumonia in China, 2019

              Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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                Author and article information

                Journal
                Science
                Science
                SCIENCE
                science
                Science (New York, N.y.)
                American Association for the Advancement of Science
                0036-8075
                1095-9203
                13 November 2020
                20 October 2020
                : 370
                : 6518
                : 856-860
                Affiliations
                [1 ]Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
                [2 ]German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
                [3 ]Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland.
                [4 ]Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
                [5 ]Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany.
                [6 ]Max Planck Institute for Experimental Medicine, Göttingen, Germany.
                [7 ]Department of Virology, Medicum, University of Helsinki, Helsinki, Finland.
                [8 ]Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
                [9 ]Helsinki Institute of Life Sciences–Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
                [10 ]Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
                [11 ]Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
                [12 ]Department of Health Security, Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
                [13 ]Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
                [14 ]Department of Anesthesiology and Intensive Care Medicine, University Medical Center Göttingen, Göttingen, Germany.
                [15 ]Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
                [16 ]Paracelsus-Elena-Klinik Kassel, Kassel, Germany.
                [17 ]Institute of Biochemistry, ETH Zürich, Zürich, Switzerland.
                [18 ]The Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
                [19 ]Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
                [20 ]Center for Nanomedicine and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
                [21 ]Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
                [22 ]Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
                [23 ]Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
                Author notes
                [*]

                These authors contributed equally to this work.

                []Corresponding author. Email: giuseppe.balistreri@ 123456helsinki.fi (G.B.); mikael.simons@ 123456dzne.de (M.S.)
                Author information
                https://orcid.org/0000-0002-0642-1610
                https://orcid.org/0000-0001-7876-4607
                https://orcid.org/0000-0003-3556-647X
                https://orcid.org/0000-0002-7759-6557
                https://orcid.org/0000-0001-7523-6622
                https://orcid.org/0000-0002-2347-5397
                https://orcid.org/0000-0002-9433-9173
                https://orcid.org/0000-0001-5926-8608
                https://orcid.org/0000-0002-4555-6446
                https://orcid.org/0000-0003-1528-044X
                https://orcid.org/0000-0003-4797-5481
                https://orcid.org/0000-0002-2229-6661
                https://orcid.org/0000-0002-4533-0455
                https://orcid.org/0000-0001-6400-1107
                https://orcid.org/0000-0001-7060-5871
                https://orcid.org/0000-0001-6319-404X
                https://orcid.org/0000-0002-9458-6385
                https://orcid.org/0000-0001-5699-214X
                https://orcid.org/0000-0003-2270-6824
                https://orcid.org/0000-0003-1766-5458
                https://orcid.org/0000-0002-3585-559X
                https://orcid.org/0000-0001-5329-192X
                Article
                abd2985
                10.1126/science.abd2985
                7857391
                33082293
                3a33cd1b-88e1-41c6-99b2-3506b8742e99
                Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

                This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 June 2020
                : 12 October 2020
                Funding
                Funded by: ERC CoV;
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