The emergence of escape-mutants of influenza hemagglutinin (HA) following vaccination compels the yearly re-formulation of flu vaccines. Since binding the sialic acid receptor remains in all cases essential for infection, small-molecule inhibitors of HA binding to sialic acid could be interesting therapeutic complements or alternatives to immuno-prophylaxis in the control of flu epidemics. In this work, we made use of NMR spectroscopy to study the interaction between a derivative of sialic acid (the Neu5Ac-α-(2,6)-Gal-β-(1-4)-GlcNAc trisaccharide) and HAs (H1 and H5) from human and avian strains of influenza virus, directly expressed on the surface of stable transfected 293 T human cells. The HAs were shown to retain their native trimeric conformation and binding properties. Exploiting the magnetization transfer between the proteins and the ligand, we obtained evidence of the binding event and mapped the (non-identical) sugar epitopes recognized by the two HA species. The rapid and reliable method for screening sialic acid-related HA ligands we have developed could yield useful information for an efficient drug design.

NMR interaction studies of Neu5Ac-α-(2,6)-Gal-β-(1-4)-GlcNAc with influenza-virus hemagglutinin expressed in transfected human cells / F. Vasile, F. Gubinelli, M. Panigada, E. Soprana, A. Siccardi, D. Potenza. - In: GLYCOBIOLOGY. - ISSN 0959-6658. - 28:1(2018), pp. 42-49. [10.1093/glycob/cwx092]

NMR interaction studies of Neu5Ac-α-(2,6)-Gal-β-(1-4)-GlcNAc with influenza-virus hemagglutinin expressed in transfected human cells

F. Vasile
;
F. Gubinelli;M. Panigada;A. Siccardi;D. Potenza
2018

Abstract

The emergence of escape-mutants of influenza hemagglutinin (HA) following vaccination compels the yearly re-formulation of flu vaccines. Since binding the sialic acid receptor remains in all cases essential for infection, small-molecule inhibitors of HA binding to sialic acid could be interesting therapeutic complements or alternatives to immuno-prophylaxis in the control of flu epidemics. In this work, we made use of NMR spectroscopy to study the interaction between a derivative of sialic acid (the Neu5Ac-α-(2,6)-Gal-β-(1-4)-GlcNAc trisaccharide) and HAs (H1 and H5) from human and avian strains of influenza virus, directly expressed on the surface of stable transfected 293 T human cells. The HAs were shown to retain their native trimeric conformation and binding properties. Exploiting the magnetization transfer between the proteins and the ligand, we obtained evidence of the binding event and mapped the (non-identical) sugar epitopes recognized by the two HA species. The rapid and reliable method for screening sialic acid-related HA ligands we have developed could yield useful information for an efficient drug design.
STD-NMR spectroscopy; anti-viral drug discovery; influenza-virus hemagglutinin; ligand-protein interaction; transfected cells
Settore CHIM/06 - Chimica Organica
2018
Article (author)
File in questo prodotto:
File Dimensione Formato  
Vasile_Glycobiol_postprint.pdf

accesso aperto

Descrizione: versione accettato
Tipologia: Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione 213.23 kB
Formato Adobe PDF
213.23 kB Adobe PDF Visualizza/Apri
cwx092.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 621.1 kB
Formato Adobe PDF
621.1 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/560236
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 17
social impact