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NOVEL ACE2-INDEPENDENT CARBOHYDRATE-BINDING OF SARS-COV-2 SPIKE PROTEIN TO HOST
LECTINS AND LUNG MICROBIOTA
View ORCID ProfileFabrizio Chiodo, Sven C.M. Bruijns, Ernesto Rodriguez, R.J.
Eveline Li, Antonio Molinaro, Alba Silipo, Flaviana Di Lorenzo, Dagmar
Garcia-Rivera, Yury Valdes-Balbin, Vicente Verez-Bencomo, Yvette van Kooyk
doi: https://doi.org/10.1101/2020.05.13.092478
This article is a preprint and has not been certified by peer review [what does
this mean?].
Fabrizio Chiodo
1Department of Molecular Cell Biology and Immunology, Amsterdam Infection &
Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije
Universiteit Amsterdam, Amsterdam, The Netherlands
3Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba
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* ORCID record for Fabrizio Chiodo
* For correspondence: f.chiodo@amsterdamumc.nl
Sven C.M. Bruijns
1Department of Molecular Cell Biology and Immunology, Amsterdam Infection &
Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije
Universiteit Amsterdam, Amsterdam, The Netherlands
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Ernesto Rodriguez
1Department of Molecular Cell Biology and Immunology, Amsterdam Infection &
Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije
Universiteit Amsterdam, Amsterdam, The Netherlands
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R.J. Eveline Li
1Department of Molecular Cell Biology and Immunology, Amsterdam Infection &
Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije
Universiteit Amsterdam, Amsterdam, The Netherlands
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Antonio Molinaro
2Department of Chemical Sciences, University of Naples Federico II, Via Cinthia
4, 80126 Naples, Italy
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Alba Silipo
2Department of Chemical Sciences, University of Naples Federico II, Via Cinthia
4, 80126 Naples, Italy
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Flaviana Di Lorenzo
2Department of Chemical Sciences, University of Naples Federico II, Via Cinthia
4, 80126 Naples, Italy
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Dagmar Garcia-Rivera
3Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba
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Yury Valdes-Balbin
3Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba
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Vicente Verez-Bencomo
3Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba
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Yvette van Kooyk
1Department of Molecular Cell Biology and Immunology, Amsterdam Infection &
Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije
Universiteit Amsterdam, Amsterdam, The Netherlands
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301012353 Comments0 TRiP Peer Reviews1 Community Reviews0 Automated Evaluations1
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ABSTRACT
The immediate call for translational research in the field of coronavirus
disease (COVID-19) pandemic, needs new and unexplored angles to support and
contribute to this important worldwide health problem. The aim of this study is
to better understand the pathogenic mechanisms underlying COVID-19, deciphering
the carbohydrate-mediated interactions of the SARS-CoV-2 spike protein. We
studied the carbohydrate-binding receptors that could be important for viral
entry and for immune-modulatory responses, and we studied the interactions of
the spike protein with the host lung microbiota. Exploring solid-phase
immunoassays, we evaluated the interactions between the SARS-CoV-2 spike protein
and a library of 12 different human carbohydrate-binding proteins (C-type
lectins and Siglecs) involved in binding, triggering and modulation of innate
and adaptive immune-responses. We revealed a specific binding of the SARS-CoV-2
spike protein to the receptors DC-SIGN, MGL, Siglec-9 and Siglec-10 that are all
expressed on myeloid immune cells. In addition, because the lung microbiota can
promote or modulate viral infection, we studied the interactions between the
SARS-CoV-2 spike protein and a library of Streptococcus pneumoniae capsular
polysaccharides, as well as other bacterial glyco-conjugates. We show specific
binding of the spike protein to different S. pneumoniae capsular polysaccharides
(serotypes 19F and 23F but not to serotype 14). Moreover we demonstrated a
specific binding of SARS-CoV-2 spike protein to the lipopolysaccharide from the
opportunistic human pathogen Pseudomonas aeruginosa, one of the leading cause of
acute nosocomial infections and pneumonia. Interestingly, we identified
rhamnosylated epitopes as one of the discriminating structures in lung
microbiota to bind SARS-CoV-2 spike protein. In conclusion, we revealed novel
ACE2-independent carbohydrate-mediated interactions with immune modulating
lectins expressed on myeloid cells, as well as host lung microbiota
glyco-conjugates. Our results identified new molecular pathways using host
lectins and signalling, that may contribute to viral infection and subsequent
immune exacerbation. Moreover we identified specific rhamnosylated epitopes in
lung microbiota to bind SARS-CoV-2, providing a hypothetical link between the
presence of specific lung microbiota and SARS-CoV-2 infection and severity.
COMPETING INTEREST STATEMENT
The authors have declared no competing interest.
Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv
Copyright
The copyright holder for this preprint is the author/funder, who has granted
bioRxiv a license to display the preprint in perpetuity. All rights reserved. No
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Posted May 14, 2020.
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Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host
Lectins and Lung Microbiota
Fabrizio Chiodo, Sven C.M. Bruijns, Ernesto Rodriguez, R.J. Eveline Li, Antonio
Molinaro, Alba Silipo, Flaviana Di Lorenzo, Dagmar Garcia-Rivera, Yury
Valdes-Balbin, Vicente Verez-Bencomo, Yvette van Kooyk
bioRxiv 2020.05.13.092478; doi: https://doi.org/10.1101/2020.05.13.092478
This article is a preprint and has not been certified by peer review [what does
this mean?].
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Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host
Lectins and Lung Microbiota
Fabrizio Chiodo, Sven C.M. Bruijns, Ernesto Rodriguez, R.J. Eveline Li, Antonio
Molinaro, Alba Silipo, Flaviana Di Lorenzo, Dagmar Garcia-Rivera, Yury
Valdes-Balbin, Vicente Verez-Bencomo, Yvette van Kooyk
bioRxiv 2020.05.13.092478; doi: https://doi.org/10.1101/2020.05.13.092478
This article is a preprint and has not been certified by peer review [what does
this mean?].
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