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Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern

Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UD...

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Autores principales: Vanhulle, Emiel, D’huys, Thomas, Provinciael, Becky, Stroobants, Joren, Camps, Anita, Noppen, Sam, Schols, Dominique, Van Damme, Els J. M., Maes, Piet, Stevaert, Annelies, Vermeire, Kurt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468479/
https://www.ncbi.nlm.nih.gov/pubmed/36111239
http://dx.doi.org/10.3389/fcimb.2022.989534
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author Vanhulle, Emiel
D’huys, Thomas
Provinciael, Becky
Stroobants, Joren
Camps, Anita
Noppen, Sam
Schols, Dominique
Van Damme, Els J. M.
Maes, Piet
Stevaert, Annelies
Vermeire, Kurt
author_facet Vanhulle, Emiel
D’huys, Thomas
Provinciael, Becky
Stroobants, Joren
Camps, Anita
Noppen, Sam
Schols, Dominique
Van Damme, Els J. M.
Maes, Piet
Stevaert, Annelies
Vermeire, Kurt
author_sort Vanhulle, Emiel
collection PubMed
description Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks transduction of pseudotyped SARS-CoV-2 in A549.ACE2(+)-TMPRSS2 cells, with IC(50) values ranging from 0.32 to 1.22 µM. Furthermore, UDA prevents viral replication of the early Wuhan-Hu-1 strain in Vero E6 cells (IC(50) = 225 nM), but also the replication of SARS-CoV-2 variants of concern, including Alpha, Beta and Gamma (IC(50) ranging from 115 to 171 nM). In addition, UDA exerts antiviral activity against the latest circulating Delta and Omicron variant in U87.ACE2(+) cells (IC(50) values are 1.6 and 0.9 µM, respectively). Importantly, when tested in Air-Liquid Interface (ALI) primary lung epithelial cell cultures, UDA preserves antiviral activity against SARS-CoV-2 (20A.EU2 variant) in the nanomolar range. Surface plasmon resonance (SPR) studies demonstrated a concentration-dependent binding of UDA to the viral spike protein of SARS-CoV-2, suggesting interference of UDA with cell attachment or subsequent virus entry. Moreover, in additional mechanistic studies with cell-cell fusion assays, UDA inhibited SARS-CoV-2 spike protein-mediated membrane fusion. Finally, pseudotyped SARS-CoV-2 mutants with N-glycosylation deletions in the S2 subunit of the spike protein remained sensitive to the antiviral activity of UDA. In conclusion, our data establish UDA as a potent fusion inhibitor for the current variants of SARS-CoV-2.
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spelling pubmed-94684792022-09-14 Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern Vanhulle, Emiel D’huys, Thomas Provinciael, Becky Stroobants, Joren Camps, Anita Noppen, Sam Schols, Dominique Van Damme, Els J. M. Maes, Piet Stevaert, Annelies Vermeire, Kurt Front Cell Infect Microbiol Cellular and Infection Microbiology Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks transduction of pseudotyped SARS-CoV-2 in A549.ACE2(+)-TMPRSS2 cells, with IC(50) values ranging from 0.32 to 1.22 µM. Furthermore, UDA prevents viral replication of the early Wuhan-Hu-1 strain in Vero E6 cells (IC(50) = 225 nM), but also the replication of SARS-CoV-2 variants of concern, including Alpha, Beta and Gamma (IC(50) ranging from 115 to 171 nM). In addition, UDA exerts antiviral activity against the latest circulating Delta and Omicron variant in U87.ACE2(+) cells (IC(50) values are 1.6 and 0.9 µM, respectively). Importantly, when tested in Air-Liquid Interface (ALI) primary lung epithelial cell cultures, UDA preserves antiviral activity against SARS-CoV-2 (20A.EU2 variant) in the nanomolar range. Surface plasmon resonance (SPR) studies demonstrated a concentration-dependent binding of UDA to the viral spike protein of SARS-CoV-2, suggesting interference of UDA with cell attachment or subsequent virus entry. Moreover, in additional mechanistic studies with cell-cell fusion assays, UDA inhibited SARS-CoV-2 spike protein-mediated membrane fusion. Finally, pseudotyped SARS-CoV-2 mutants with N-glycosylation deletions in the S2 subunit of the spike protein remained sensitive to the antiviral activity of UDA. In conclusion, our data establish UDA as a potent fusion inhibitor for the current variants of SARS-CoV-2. Frontiers Media S.A. 2022-08-30 /pmc/articles/PMC9468479/ /pubmed/36111239 http://dx.doi.org/10.3389/fcimb.2022.989534 Text en Copyright © 2022 Vanhulle, D’huys, Provinciael, Stroobants, Camps, Noppen, Schols, Van Damme, Maes, Stevaert and Vermeire 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 Cellular and Infection Microbiology
Vanhulle, Emiel
D’huys, Thomas
Provinciael, Becky
Stroobants, Joren
Camps, Anita
Noppen, Sam
Schols, Dominique
Van Damme, Els J. M.
Maes, Piet
Stevaert, Annelies
Vermeire, Kurt
Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern
title Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern
title_full Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern
title_fullStr Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern
title_full_unstemmed Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern
title_short Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern
title_sort carbohydrate-binding protein from stinging nettle as fusion inhibitor for sars-cov-2 variants of concern
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468479/
https://www.ncbi.nlm.nih.gov/pubmed/36111239
http://dx.doi.org/10.3389/fcimb.2022.989534
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