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Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2

  1. Author:
    Muñoz-Basagoiti, Jordana [ORCID]
    Monteiro, Fábio Luís Lima [ORCID]
    Haugh Krumpe,Lauren [ORCID]
    Armario-Najera, Victoria [ORCID]
    Shenoy, Shilpa R
    Perez-Zsolt, Daniel
    Westgarth, Harrison James
    Villorbina, Gemma [ORCID]
    Bomfim, Larissa Maciel
    Raïch-Regué, Dàlia
    Nogueras, Lara
    Henrich,Curtis [ORCID]
    Gallemí, Marçal
    Moreira, Filipe Romero Rebello
    Torres, Pascual [ORCID]
    Wilson,Jennifer [ORCID]
    D'arc, Mirela [ORCID]
    Marfil, Silvia [ORCID]
    Herlinger, Alice Laschuk [ORCID]
    Pradenas, Edwards [ORCID]
    Higa, Luiza Mendonça
    Portero-Otin, Manuel [ORCID]
    Trinité, Benjamin
    Twyman, Richard M [ORCID]
    Capell, Teresa
    Tanuri, Amilcar
    Blanco, Julià [ORCID]
    Izquierdo-Useros, Nuria [ORCID]
    Rech, Elibio L [ORCID]
    Christou, Paul
    O'Keefe,Barry
  2. Author Address

    IrsiCaixa Acquired Immune Deficiency Syndrome Research Institute, Badalona 08916, Spain., Laboratory of Molecular Virology, Institute of Biology, Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-90, Brazil., Molecular Targets Program, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, MD 21702., Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Department of Crop and Forest Sciences, University of Lleida-Agrotecnio Center, Lleida 25198, Spain., Laboratory of Diversity and Viral Diseases, Institute of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-90, Brazil., Twyman Research Management Ltd, Scarborough YO11 9FJ, UK., Germans Trias i Pujol Research Institute, Badalona 08916, Spain., Centro de Investigaci 243;n Biom 233;dica en Red Enfermedades Infecciosas, Madrid 28029, Spain., Universitat de Vic - Universitat Central de Catalunya, Vic 08500, Spain., Embrapa Genetic Resources and Biotechnology National Institute of Science and Technology in Synthetic Biology, Bras 237;lia 70770-917, Brazil., ICREA, Catalan Institute for Research and Advanced Studies, Barcelona 08010, Spain., Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702.,
    1. Year: 2023
    2. Date: Mar 07
    3. Epub Date: 2023 02 28
  1. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 120
    2. 10
    3. Pages: e2214561120
  2. Type of Article: Article
  3. Article Number: e2214561120
  1. Abstract:

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and cyanobacteria. Some lectins can neutralize enveloped viruses displaying external glycoproteins, offering an alternative therapeutic approach for the prevention of infection with virulent ß-coronaviruses, such as SARS-CoV-2. Here we show that the cyanobacterial lectin cyanovirin-N (CV-N) can selectively target SARS-CoV-2 Spike oligosaccharides and inhibit SARS-CoV-2 infection in 160;vitro and in 160;vivo. CV-N neutralizes Delta and Omicron variants in 160;vitro better than earlier circulating viral variants. CV-N binds selectively to Spike with a Kd as low as 15 nM and a stoichiometry of 2 CV-N: 1 Spike but does not bind to the receptor binding domain (RBD). Further mapping of CV-N binding sites on Spike shows that select high-mannose oligosaccharides in the S1 domain of Spike are targeted by CV-N. CV-N also reduced viral loads in the nares and lungs in 160;vivo to protect hamsters against a lethal viral challenge. In summary, we present an anti-coronavirus agent that works by an unexploited mechanism and prevents infection by a broad range of SARS-CoV-2 strains.

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External Sources

  1. DOI: 10.1073/pnas.2214561120
  2. PMID: 36853940

Library Notes

  1. Fiscal Year: FY2022-2023
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