Format

Send to

Choose Destination
PLoS Pathog. 2012;8(10):e1002976. doi: 10.1371/journal.ppat.1002976. Epub 2012 Oct 25.

Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

Author information

1
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

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.

PMID:
23133371
PMCID:
PMC3486884
DOI:
10.1371/journal.ppat.1002976
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center