A combined nmr-computational study of the interaction between influenza virus hemagglutinin and sialic derivatives from human and avian receptors on the surface of transfected cells

F Vasile, M Panigada, A Siccardi, D Potenza, G Tiana

Research output: Contribution to journalArticle

Abstract

The development of small-molecule inhibitors of influenza virus Hemagglutinin could be relevant to the opposition of the diffusion of new pandemic viruses. In this work, we made use of Nuclear Magnetic Resonance (NMR) spectroscopy to study the interaction between two derivatives of sialic acid, Neu5Ac-α-(2,6)-Gal- β -(1–4)-GlcNAc and Neu5Ac- α -(2,3)-Gal- β -(1–4)-GlcNAc, and hemagglutinin directly expressed on the surface of recombinant human cells. We analyzed the interaction of these trisaccharides with 293T cells transfected with the H5 and H1 variants of hemagglutinin, which thus retain their native trimeric conformation in such a realistic environment. By exploiting the magnetization transfer between the protein and the ligand, we obtained evidence of the binding event, and identified the epitope. We analyzed the conformational features of the glycans with an approach combining NMR spectroscopy and data-driven molecular dynamics simulations, thus obtaining useful information for an efficient drug design. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
Article number1267
JournalInternational Journal of Molecular Sciences
Volume19
Issue number5
DOIs
Publication statusPublished - 2018

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influenza
magnetic resonance spectroscopy
Hemagglutinins
viruses
Orthomyxoviridae
Viruses
Saliva
Nuclear magnetic resonance spectroscopy
Derivatives
Epitopes
nuclear magnetic resonance
Magnetic Resonance Spectroscopy
cells
Switzerland
inhibitors
Conformations
Molecular dynamics
Trisaccharides
Magnetization
drugs

Cite this

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title = "A combined nmr-computational study of the interaction between influenza virus hemagglutinin and sialic derivatives from human and avian receptors on the surface of transfected cells",
abstract = "The development of small-molecule inhibitors of influenza virus Hemagglutinin could be relevant to the opposition of the diffusion of new pandemic viruses. In this work, we made use of Nuclear Magnetic Resonance (NMR) spectroscopy to study the interaction between two derivatives of sialic acid, Neu5Ac-α-(2,6)-Gal- β -(1–4)-GlcNAc and Neu5Ac- α -(2,3)-Gal- β -(1–4)-GlcNAc, and hemagglutinin directly expressed on the surface of recombinant human cells. We analyzed the interaction of these trisaccharides with 293T cells transfected with the H5 and H1 variants of hemagglutinin, which thus retain their native trimeric conformation in such a realistic environment. By exploiting the magnetization transfer between the protein and the ligand, we obtained evidence of the binding event, and identified the epitope. We analyzed the conformational features of the glycans with an approach combining NMR spectroscopy and data-driven molecular dynamics simulations, thus obtaining useful information for an efficient drug design. {\circledC} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",
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T1 - A combined nmr-computational study of the interaction between influenza virus hemagglutinin and sialic derivatives from human and avian receptors on the surface of transfected cells

AU - Vasile, F

AU - Panigada, M

AU - Siccardi, A

AU - Potenza, D

AU - Tiana, G

PY - 2018

Y1 - 2018

N2 - The development of small-molecule inhibitors of influenza virus Hemagglutinin could be relevant to the opposition of the diffusion of new pandemic viruses. In this work, we made use of Nuclear Magnetic Resonance (NMR) spectroscopy to study the interaction between two derivatives of sialic acid, Neu5Ac-α-(2,6)-Gal- β -(1–4)-GlcNAc and Neu5Ac- α -(2,3)-Gal- β -(1–4)-GlcNAc, and hemagglutinin directly expressed on the surface of recombinant human cells. We analyzed the interaction of these trisaccharides with 293T cells transfected with the H5 and H1 variants of hemagglutinin, which thus retain their native trimeric conformation in such a realistic environment. By exploiting the magnetization transfer between the protein and the ligand, we obtained evidence of the binding event, and identified the epitope. We analyzed the conformational features of the glycans with an approach combining NMR spectroscopy and data-driven molecular dynamics simulations, thus obtaining useful information for an efficient drug design. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

AB - The development of small-molecule inhibitors of influenza virus Hemagglutinin could be relevant to the opposition of the diffusion of new pandemic viruses. In this work, we made use of Nuclear Magnetic Resonance (NMR) spectroscopy to study the interaction between two derivatives of sialic acid, Neu5Ac-α-(2,6)-Gal- β -(1–4)-GlcNAc and Neu5Ac- α -(2,3)-Gal- β -(1–4)-GlcNAc, and hemagglutinin directly expressed on the surface of recombinant human cells. We analyzed the interaction of these trisaccharides with 293T cells transfected with the H5 and H1 variants of hemagglutinin, which thus retain their native trimeric conformation in such a realistic environment. By exploiting the magnetization transfer between the protein and the ligand, we obtained evidence of the binding event, and identified the epitope. We analyzed the conformational features of the glycans with an approach combining NMR spectroscopy and data-driven molecular dynamics simulations, thus obtaining useful information for an efficient drug design. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

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