Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

  1. Matteo Stravalaci
  2. Isabel Pagani
  3. Elvezia Maria Paraboschi
  4. Mattia Pedotti
  5. Andrea Doni
  6. Francesco Scavello
  7. Sarah N. Mapelli
  8. Marina Sironi
  9. Luca Varani
  10. Milos Matkovic
  11. Andrea Cavalli
  12. Daniela Cesana
  13. Pierangela Gallina
  14. Nicoletta Pedemonte
  15. Valeria Capurro
  16. Nicola Clementi
  17. Nicasio Mancini
  18. Pietro Invernizzi
  19. Rino Rappuoli
  20. Stefano Duga
  21. Barbara Bottazzi
  22. Mariagrazia Uguccioni
  23. Rosanna Asselta
  24. Elisa Vicenzi
  25. Alberto Mantovani
  26. Cecilia Garlanda
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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 threein vitromodels. 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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