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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Cell Line
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Cell Membrane / chemistry
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Cell Membrane / drug effects
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Cells, Cultured
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Cholestanols / chemistry
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Cholestanols / pharmacology
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Cricetinae
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Female
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Hepatitis B virus / drug effects
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Hepatitis B virus / growth & development
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Hepatitis Delta Virus / drug effects
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Hepatitis Delta Virus / growth & development
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Hepatocytes / drug effects
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Hepatocytes / virology
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Humans
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Male
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Mesocricetus
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Mice
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Mice, Inbred BALB C
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Molecular Structure
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Muromegalovirus / drug effects
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Muromegalovirus / growth & development
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Scattering, Small Angle
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Virus Diseases / drug therapy*
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Virus Diseases / virology
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Virus Replication / drug effects*
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X-Ray Diffraction
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rac1 GTP-Binding Protein / chemistry
Substances
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Anti-Bacterial Agents
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Antiviral Agents
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Cholestanols
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rac1 GTP-Binding Protein
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squalamine