Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses.

Details

Serval ID
serval:BIB_CF22445F5B5E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses.
Journal
Viruses
Author(s)
Mayor J., Torriani G., Engler O., Rothenberger S.
ISSN
1999-4915 (Electronic)
ISSN-L
1999-4915
Publication state
Published
Issued date
16/04/2021
Peer-reviewed
Oui
Volume
13
Number
4
Pages
685
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
Antiviral Agents/therapeutic use, Drug Evaluation, Preclinical/methods, Orthohantavirus/drug effects, Hantavirus Infections/drug therapy, Humans, Virus Internalization/drug effects, GFP, antiviral screening, arenavirus, ebolavirus, entry inhibitors, orthohantaviruses, viral hemorrhagic fever
Pubmed
Web of science
Open Access
Yes
Create date
30/04/2021 16:58
Last modification date
30/12/2023 7:08
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