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Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses

Hemorrhagic fever viruses, among them orthohantaviruses, arenaviruses and filoviruses, are responsible for some of the most severe human diseases and represent a serious challenge for public health. The current limited therapeutic options and available vaccines make the development of novel efficaci...

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Autores principales: Mayor, Jennifer, Torriani, Giulia, Engler, Olivier, Rothenberger, Sylvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074185/
https://www.ncbi.nlm.nih.gov/pubmed/33923413
http://dx.doi.org/10.3390/v13040685
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author Mayor, Jennifer
Torriani, Giulia
Engler, Olivier
Rothenberger, Sylvia
author_facet Mayor, Jennifer
Torriani, Giulia
Engler, Olivier
Rothenberger, Sylvia
author_sort Mayor, Jennifer
collection PubMed
description Hemorrhagic fever viruses, among them orthohantaviruses, arenaviruses and filoviruses, are responsible for some of the most severe human diseases and represent a serious challenge for public health. The current limited therapeutic options and available vaccines make the development of novel efficacious antiviral agents an urgent need. Inhibiting viral attachment and entry is a promising strategy for the development of new treatments and to prevent all subsequent steps in virus infection. Here, we developed a fluorescence-based screening assay for the identification of new antivirals against hemorrhagic fever virus entry. We screened a phytochemical library containing 320 natural compounds using a validated VSV pseudotype platform bearing the glycoprotein of the virus of interest and encoding enhanced green fluorescent protein (EGFP). EGFP expression allows the quantitative detection of infection and the identification of compounds affecting viral entry. We identified several hits against four pseudoviruses for the orthohantaviruses Hantaan (HTNV) and Andes (ANDV), the filovirus Ebola (EBOV) and the arenavirus Lassa (LASV). Two selected inhibitors, emetine dihydrochloride and tetrandrine, were validated with infectious pathogenic HTNV in a BSL-3 laboratory. This study provides potential therapeutics against emerging virus infection, and highlights the importance of drug repurposing.
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spelling pubmed-80741852021-04-27 Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses Mayor, Jennifer Torriani, Giulia Engler, Olivier Rothenberger, Sylvia Viruses Article Hemorrhagic fever viruses, among them orthohantaviruses, arenaviruses and filoviruses, are responsible for some of the most severe human diseases and represent a serious challenge for public health. The current limited therapeutic options and available vaccines make the development of novel efficacious antiviral agents an urgent need. Inhibiting viral attachment and entry is a promising strategy for the development of new treatments and to prevent all subsequent steps in virus infection. Here, we developed a fluorescence-based screening assay for the identification of new antivirals against hemorrhagic fever virus entry. We screened a phytochemical library containing 320 natural compounds using a validated VSV pseudotype platform bearing the glycoprotein of the virus of interest and encoding enhanced green fluorescent protein (EGFP). EGFP expression allows the quantitative detection of infection and the identification of compounds affecting viral entry. We identified several hits against four pseudoviruses for the orthohantaviruses Hantaan (HTNV) and Andes (ANDV), the filovirus Ebola (EBOV) and the arenavirus Lassa (LASV). Two selected inhibitors, emetine dihydrochloride and tetrandrine, were validated with infectious pathogenic HTNV in a BSL-3 laboratory. This study provides potential therapeutics against emerging virus infection, and highlights the importance of drug repurposing. MDPI 2021-04-16 /pmc/articles/PMC8074185/ /pubmed/33923413 http://dx.doi.org/10.3390/v13040685 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mayor, Jennifer
Torriani, Giulia
Engler, Olivier
Rothenberger, Sylvia
Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses
title Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses
title_full Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses
title_fullStr Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses
title_full_unstemmed Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses
title_short Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses
title_sort identification of novel antiviral compounds targeting entry of hantaviruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074185/
https://www.ncbi.nlm.nih.gov/pubmed/33923413
http://dx.doi.org/10.3390/v13040685
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