Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-66209

Jurgeit, Andreas; McDowell, Robert; Moese, Stefan; Meldrum, Eric; Schwendener, Reto; Greber, Urs F (2012). Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects. PLoS Pathogens, 8(10):e1002976.

[img]
Preview
Published Version (English)
PDF
1MB

Abstract

Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H+-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research

07 Faculty of Science > Institute of Molecular Life Sciences
Special Collections > SystemsX.ch > Research, Technology and Development Projects > InfectX
DDC:570 Life sciences; biology
Language:English
Date:25 October 2012
Deposited On:06 Nov 2012 16:31
Last Modified:28 Nov 2013 01:35
Publisher:Public Library of Science
ISSN:1553-7366
Publisher DOI:10.1371/journal.ppat.1002976
Citations:Web of Science®. Times Cited: 7
Google Scholar™
Scopus®. Citation Count: 7

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page