title: Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential.
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.
authors.affiliation: Transplant Institute, Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Zasloff
authors.forename: A Paige
authors.initials: AP
authors.lastname: Adams
authors.forename: Bernard
authors.initials: B
authors.lastname: Beckerman
authors.forename: Ann
authors.initials: A
authors.lastname: Campbell
authors.forename: Ziying
authors.initials: Z
authors.lastname: Han
authors.forename: Erik
authors.initials: E
authors.lastname: Luijten
authors.forename: Isaura
authors.initials: I
authors.lastname: Meza
authors.forename: Justin
authors.initials: J
authors.lastname: Julander
authors.forename: Abhijit
authors.initials: A
authors.lastname: Mishra
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: John M
authors.initials: JM
authors.lastname: Taylor
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.forename: Gerard C L
authors.initials: GC
authors.lastname: Wong
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D002478:Cells, Cultured; D002777:Cholestanols / Q000737:chemistry / Q000494:pharmacology; D006224:Cricetinae; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000254:growth & development; D003698:Hepatitis Delta Virus / Q000187:drug effects / Q000254:growth & development; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D018146:Muromegalovirus / Q000187:drug effects / Q000254:growth & development; D053838:Scattering, Small Angle; D014777:Virus Diseases / Q000188:drug therapy* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*; D014961:X-Ray Diffraction; D020830:rac1 GTP-Binding Protein / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D002777:Cholestanols; D020830:rac1 GTP-Binding Protein; C079655:squalamine