Premium
Evidence for Multiple Binding Modes in the Initial Contact Between SARS‐CoV‐2 Spike S1 Protein and Cell Surface Glycans **
Author(s) -
Parafioriti Michela,
Ni Minghong,
Petitou Maurice,
MycroftWest Courtney J.,
Rudd Timothy R.,
Gandhi Neha S.,
Ferro Vito,
Turnbull Jeremy E.,
Lima Marcelo A.,
Skidmore Mark A.,
Fernig David G.,
Yates Edwin A.,
Bisio Antonella,
Guerrini Marco,
Elli Stefano
Publication year - 2023
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202202599
Subject(s) - spike (software development) , glycan , surface protein , biophysics , spike protein , covid-19 , surface (topology) , plasma protein binding , chemistry , computational biology , biology , microbiology and biotechnology , virology , computer science , biochemistry , glycoprotein , medicine , mathematics , geometry , software engineering , disease , pathology , infectious disease (medical specialty)
Infection of host cells by SARS‐CoV‐2 begins with recognition by the virus S (spike) protein of cell surface heparan sulfate (HS), tethering the virus to the extracellular matrix environment, and causing the subunit S1‐RBD to undergo a conformational change into the ‘open’ conformation. These two events promote the binding of S1‐RBD to the angiotensin converting enzyme 2 (ACE2) receptor, a preliminary step toward viral‐cell membrane fusion. Combining ligand‐based NMR spectroscopy with molecular dynamics, oligosaccharide analogues were used to explore the interactions between S1‐RBD of SARS CoV‐2 and HS, revealing several low‐specificity binding modes and previously unidentified potential sites for the binding of extended HS polysaccharide chains. The evidence for multiple binding modes also suggest that highly specific inhibitors will not be optimal against protein S but, rather, diverse HS‐based structures, characterized by high affinity and including multi‐valent compounds, may be required.