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Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach

Recent experimental evidence demonstrated the capability of SARS-CoV-2 Spike protein to bind sialic acid molecules, which was a trait not present in SARS-CoV and could shed light on the molecular mechanism used by the virus for the cell invasion. This peculiar feature has been successfully predicted...

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Autores principales: Bò, Leonardo, Miotto, Mattia, Di Rienzo, Lorenzo, Milanetti, Edoardo, Ruocco, Giancarlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757799/
https://www.ncbi.nlm.nih.gov/pubmed/35047894
http://dx.doi.org/10.3389/fmedt.2020.614652
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author Bò, Leonardo
Miotto, Mattia
Di Rienzo, Lorenzo
Milanetti, Edoardo
Ruocco, Giancarlo
author_facet Bò, Leonardo
Miotto, Mattia
Di Rienzo, Lorenzo
Milanetti, Edoardo
Ruocco, Giancarlo
author_sort Bò, Leonardo
collection PubMed
description Recent experimental evidence demonstrated the capability of SARS-CoV-2 Spike protein to bind sialic acid molecules, which was a trait not present in SARS-CoV and could shed light on the molecular mechanism used by the virus for the cell invasion. This peculiar feature has been successfully predicted by in-silico studies comparing the sequence and structural characteristics that SARS-CoV-2 shares with other sialic acid-binding viruses, like MERS-CoV. Even if the region of the binding has been identified in the N-terminal domain of Spike protein, so far no comprehensive analyses have been carried out on the spike-sialic acid conformations once in the complex. Here, we addressed this aspect performing an extensive molecular dynamics simulation of a system composed of the N-terminal domain of the spike protein and a sialic acid molecule. We observed several short-lived binding events, reconnecting to the avidic nature of the binding, interestingly occurring in the surface Spike region where several insertions are present with respect to the SARS-CoV sequence. Characterizing the bound configurations via a clustering analysis on the Principal Component of the motion, we identified different possible binding conformations and discussed their dynamic and structural properties. In particular, we analyze the correlated motion between the binding residues and the binding effect on the stability of atomic fluctuation, thus proposing regions with high binding propensity with sialic acid.
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spelling pubmed-87577992022-01-18 Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach Bò, Leonardo Miotto, Mattia Di Rienzo, Lorenzo Milanetti, Edoardo Ruocco, Giancarlo Front Med Technol Medical Technology Recent experimental evidence demonstrated the capability of SARS-CoV-2 Spike protein to bind sialic acid molecules, which was a trait not present in SARS-CoV and could shed light on the molecular mechanism used by the virus for the cell invasion. This peculiar feature has been successfully predicted by in-silico studies comparing the sequence and structural characteristics that SARS-CoV-2 shares with other sialic acid-binding viruses, like MERS-CoV. Even if the region of the binding has been identified in the N-terminal domain of Spike protein, so far no comprehensive analyses have been carried out on the spike-sialic acid conformations once in the complex. Here, we addressed this aspect performing an extensive molecular dynamics simulation of a system composed of the N-terminal domain of the spike protein and a sialic acid molecule. We observed several short-lived binding events, reconnecting to the avidic nature of the binding, interestingly occurring in the surface Spike region where several insertions are present with respect to the SARS-CoV sequence. Characterizing the bound configurations via a clustering analysis on the Principal Component of the motion, we identified different possible binding conformations and discussed their dynamic and structural properties. In particular, we analyze the correlated motion between the binding residues and the binding effect on the stability of atomic fluctuation, thus proposing regions with high binding propensity with sialic acid. Frontiers Media S.A. 2021-01-13 /pmc/articles/PMC8757799/ /pubmed/35047894 http://dx.doi.org/10.3389/fmedt.2020.614652 Text en Copyright © 2021 Bò, Miotto, Di Rienzo, Milanetti and Ruocco. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medical Technology
Bò, Leonardo
Miotto, Mattia
Di Rienzo, Lorenzo
Milanetti, Edoardo
Ruocco, Giancarlo
Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach
title Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach
title_full Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach
title_fullStr Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach
title_full_unstemmed Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach
title_short Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach
title_sort exploring the association between sialic acid and sars-cov-2 spike protein through a molecular dynamics-based approach
topic Medical Technology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757799/
https://www.ncbi.nlm.nih.gov/pubmed/35047894
http://dx.doi.org/10.3389/fmedt.2020.614652
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