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

Michael Zasloff, A. Paige Adams, Bernard Beckerman, Ann Campbell, Ziying Han, Erik Luijten, Isaura Meza, Justin Julander, Abhijit Mishra, Wei Qu, John M. Taylor, Scott Weaver, Gerard C L Wong

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)15978-15983
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number38
DOIs
StatePublished - Oct 20 2011

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Petromyzon
Antiviral Agents
Squalus acanthias
Dogfish
Sharks
Intracellular Membranes
DNA Viruses
Sterols
Static Electricity
Human Activities
Therapeutics
RNA
Safety
squalamine

Keywords

  • Dengue virus
  • Eastern equine encephalitis virus
  • Hepatitis B virus
  • Innate immunity
  • Yellow fever virus

ASJC Scopus subject areas

  • General

Cite this

Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential. / Zasloff, Michael; Adams, A. Paige; Beckerman, Bernard; Campbell, Ann; Han, Ziying; Luijten, Erik; Meza, Isaura; Julander, Justin; Mishra, Abhijit; Qu, Wei; Taylor, John M.; Weaver, Scott; Wong, Gerard C L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 38, 20.10.2011, p. 15978-15983.

Research output: Contribution to journalArticle

Zasloff, M, Adams, AP, Beckerman, B, Campbell, A, Han, Z, Luijten, E, Meza, I, Julander, J, Mishra, A, Qu, W, Taylor, JM, Weaver, S & Wong, GCL 2011, 'Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 38, pp. 15978-15983. https://doi.org/10.1073/pnas.1108558108
Zasloff, Michael ; Adams, A. Paige ; Beckerman, Bernard ; Campbell, Ann ; Han, Ziying ; Luijten, Erik ; Meza, Isaura ; Julander, Justin ; Mishra, Abhijit ; Qu, Wei ; Taylor, John M. ; Weaver, Scott ; Wong, Gerard C L. / Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 38. pp. 15978-15983.
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