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      headline:Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules
      description:The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications. Stravalaci et al. examined recognition of SARS-CoV-2 by human soluble innate pattern recognition receptor. They report that pentraxin 3 and mannose-binding protein recognize viral nucleoprotein and spike, respectively. Mannose-binding lectin has antiviral activity, and human genetic polymorphisms of MBL2 are associated with more severe COVID-19.
      datePublished:2022-01-31T00:00:00Z
      dateModified:2022-01-31T00:00:00Z
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         Complement cascade
         Pattern recognition receptors
         Viral infection
         Biomedicine
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         Immunology
         Infectious Diseases
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            type:Organization
            name:Humanitas University
            address:
               name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Elisa Vicenzi
      url:http://orcid.org/0000-0003-0051-3968
      affiliation:
            name:IRCCS San Raffaele Scientific Institute
            address:
               name:Viral Pathogenesis and Biosafety Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Alberto Mantovani
      url:http://orcid.org/0000-0001-5578-236X
      affiliation:
            name:IRCCS Humanitas Research Hospital
            address:
               name:IRCCS Humanitas Research Hospital, Milan, Italy
               type:PostalAddress
            type:Organization
            name:Humanitas University
            address:
               name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
               type:PostalAddress
            type:Organization
            name:Queen Mary University of London, Charterhouse Square
            address:
               name:The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Cecilia Garlanda
      url:http://orcid.org/0000-0002-1510-7703
      affiliation:
            name:IRCCS Humanitas Research Hospital
            address:
               name:IRCCS Humanitas Research Hospital, Milan, Italy
               type:PostalAddress
            type:Organization
            name:Humanitas University
            address:
               name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
      name:Viral Pathogenesis and Biosafety Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
      name:Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
      name:Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
      name:Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
      name:Swiss Institute of Bioinformatics, Lausanne, Switzerland
      name:San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Milan, Italy
      name:San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Milan, Italy
      name:UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, Genova, Italy
      name:UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, Genova, Italy
      name:Laboratory of Microbiology and Virology, IRCCS Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy
      name:Laboratory of Microbiology and Virology, IRCCS Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy
      name:Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
      name:European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
      name:Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, København, Denmark
      name:Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, København, Denmark
      name:Monoclonal Antibody Discovery Lab, Fondazione Toscana Life Sciences, Siena, Italy
      name:Faculty of Medicine, Imperial College London, London, UK
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
      name:Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
      name:Viral Pathogenesis and Biosafety Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Milan, Italy
      name:The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, UK
      name:IRCCS Humanitas Research Hospital, Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Milan, Italy

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