Shark Lipid Repels Virus

Sharks have an uncanny ability to fend off viral infections, and that resistance might come courtesy of a cationic sterol molecule in their tissues, according to a study (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1108558108). The work suggests the lipid natural product squalamine could be a lead for novel antiviral agents. Originally isolated from dogfish sharks, squalamine has already been tested on humans as a treatment for nonviral diseases, according to Michael Zasloff of Georgetown University Medical Center, who led the study. Rather than inhibiting a viral enzyme, squalamine seems to exert its antiviral effects by interacting with the host cells, the researchers found. Using X-ray diffraction and molecular dynamics simulations, they showed that the lipid can displace a protein called Rac1 from the membranes of host cells. Viruses often rely upon that protein for assistance when entering cells. The researchers also showed in vitro that squalamine prevents infections by the dengue virus and two types of hepatitis. It also protected live rodents from yellow fever, cytomegalovirus, and encephalitis. However, the compound showed some signs of toxicity when it was introduced to liver cells at high doses.