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Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules
Matteo Stravalaci; Isabel Pagani; Elvezia Maria Paraboschi; Mattia Pedotti; Andrea Doni; Francesco Scavello; Sarah N. Mapelli; Marina Sironi; Luca Varani; Milos Matkovic; Andrea Cavalli; Daniela Cesana; Pierangela Gallina; Nicoletta Pedemonte; Valeria Capurro; Nicola Clementi; Nicasio Mancini; Pietro Invernizzi; Rino Rappuoli; Stefano Duga; Barbara Bottazzi; Mariagrazia Uguccioni; Rosanna Asselta; Elisa Vicenzi; Alberto Mantovani; Cecilia Garlanda.
Affiliation
  • Matteo Stravalaci; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano (Milan), Italy; Dept. Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, 2
  • Isabel Pagani; Viral Pathogenesis and Biosafety Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • Elvezia Maria Paraboschi; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano (Milan), Italy; Dept. Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, 20
  • Mattia Pedotti; Institute for Research in Biomedicine, Universita della Svizzera Italiana, Bellinzona, Switzerland
  • Andrea Doni; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano (Milan), Italy;
  • Francesco Scavello; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano (Milan), Italy;
  • Sarah N. Mapelli; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano (Milan), Italy;
  • Marina Sironi; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano (Milan), Italy;
  • Luca Varani; Institute for Research in Biomedicine, Universita della Svizzera Italiana, Bellinzona, Switzerland
  • Milos Matkovic; Institute for Research in Biomedicine, Universita della Svizzera italiana (USI), Bellinzona, Switzerland
  • Andrea Cavalli; Institute for Research in Biomedicine, Universita della Svizzera italiana (USI), Bellinzona, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerla
  • Daniela Cesana; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget); IRCCS, San Raffaele Scientific Institute, Milan, Italy
  • Pierangela Gallina; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget); IRCCS, San Raffaele Scientific Institute, Milan, Italy
  • Nicoletta Pedemonte; UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, Via Gaslini 5, 16147 Genova
  • Valeria Capurro; UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, Via Gaslini 5, 16147 Genova
  • Nicola Clementi; Laboratory of Microbiology and Virology, IRCCS Scientific Institute and Vita-Salute San Raffaele University, Milan Italy
  • Nicasio Mancini; Laboratory of Microbiology and Virology, IRCCS Scientific Institute and Vita-Salute San Raffaele University, Milan Italy
  • Pietro Invernizzi; 9Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Re
  • Rino Rappuoli; Monoclonal Antibody Discovery Lab, Fondazione Toscana Life Sciences, Siena, Italy; Faculty of Medicine, Imperial College London, London, UK
  • Stefano Duga; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano (Milan), Italy; Dept Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 200
  • Barbara Bottazzi; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano (Milan), Italy
  • Mariagrazia Uguccioni; Institute for Research in Biomedicine, Universita della Svizzera italiana (USI), Bellinzona, Switzerland; Dept Biomedical Sciences, Humanitas University, Via Ri
  • Rosanna Asselta; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano (Milan), Italy; Dept Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 200
  • Elisa Vicenzi; Viral Pathogenesis and Biosafety Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • Alberto Mantovani; IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy; Dept Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy; The William Harvey Res
  • Cecilia Garlanda; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano (Milan), Italy; Dept Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 200
Preprint in English | medRxiv | ID: ppmedrxiv-21258350
Journal article
A scientific journal published article is available and is probably based on this preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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ABSTRACT
The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in COVID-19. The present study was designed to conduct a systematic investigation of the interaction of humoral fluid phase pattern recognition molecules (PRM) with SARS-CoV-2. Out of 10 PRM tested, the long pentraxin PTX3 and Mannose Binding Lectin (MBL) bound the viral Nucleoprotein and Spike, respectively. MBL bound trimeric Spike, including that of variants of concern, in a glycan- dependent way and inhibited SARS-CoV-2 in three in vitro models. Moreover, upon binding to Spike, MBL activated the lectin pathway of complement activation. Genetic polymorphisms at the MBL locus were associated with disease severity. These results suggest that selected humoral fluid phase PRM can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.
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Full text: Available Collection: Preprints Database: medRxiv Type of study: Prognostic study / Systematic review Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: medRxiv Type of study: Prognostic study / Systematic review Language: English Year: 2021 Document type: Preprint
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