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

doi:10.1073/pnas.1108558108

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

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

95 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 language	English (US)
Pages (from-to)	15978-15983
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	108
Issue number	38
DOIs	https://doi.org/10.1073/pnas.1108558108
State	Published - 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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10.1073/pnas.1108558108

Cite this

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

Zasloff, M, Adams, AP, Beckerman, B, Campbell, A, Han, Z, Luijten, E, Meza, I, Julander, J, Mishra, A, Qu, W, Taylor, JM, Weaver, SC & 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

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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.",

keywords = "Dengue virus, Eastern equine encephalitis virus, Hepatitis B virus, Innate immunity, Yellow fever virus",

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

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AU - Adams, A. Paige

AU - Beckerman, Bernard

AU - Campbell, Ann

AU - Han, Ziying

AU - Luijten, Erik

AU - Meza, Isaura

AU - Julander, Justin

AU - Mishra, Abhijit

AU - Qu, Wei

AU - Taylor, John M.

AU - Weaver, Scott C.

AU - Wong, Gerard C.L.

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N2 - 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.

AB - 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.

KW - Dengue virus

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

Abstract

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