Giuseppe
Emeritus
[Source: Proc Natl Acad Sci USA, full text: (LINK). Abstract, edited.]
Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential [Immunology]
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.
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.
- -------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.
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.