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Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15978-83. doi: 10.1073/pnas.1108558108. Epub 2011 Sep 19.

Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential.

Author information

  • 1Transplant Institute, Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.

Erratum in

  • Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18186.

Abstract

Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human antiviral agent should be explored.

Comment in

PMID:
21930925
[PubMed - indexed for MEDLINE]
PMCID:
PMC3179074
Free PMC Article
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