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 C. Weaver, Gerard C.L. Wong

*Corresponding author for this work

Research output: Contribution to journalArticle

62 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • General

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    Zasloff, M., Adams, A. P., Beckerman, B., Campbell, A., Han, Z., Luijten, E., Meza, I., Julander, J., Mishra, A., Qu, W., Taylor, J. M., Weaver, S. C., & Wong, G. C. L. (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, 108(38), 15978-15983. https://doi.org/10.1073/pnas.1108558108