Antivirals inspired by the shark’s immune system

No one understands why sharks are such hardy animals. It turns out that they have an unusual immune system. A team from the UCLA bioengineering department led by Gerard Wong participated in a multi-national collaboration that identified a new broad spectrum systemic antiviral agent, squalamine, which is isolated from sharks. In tissue cultures, the compound inhibited the infection of blood vessel cells by the dengue virus, and human liver cells by the viruses for hepatitis B and D. Moreover, animal studies indicated that squalamine can control infections by the virus responsible for yellow fever, the eastern equine encephalitis virus, and the murine cytomegalovirus. Studies at UCLA and Northwestern showed that the antiviral effect likely came from an electrostatic remodeling of the membrane by squalamine, which can temporarily turn off endocytosis. The figure below shows that squalamine (pink) can displace Rac1 (blue), which is part of the cellular machinery for endocytosis, from membranes. The multi-institutional research team was led by Michael Zasloff from the Georgetown University Medical Center. This work was published in the Proceedings of the National Academy of Science in 2011, and has been covered extensively by the popular press, including the LA Times, BBC, and National Geographic.

Link to PDF file on website: Zasloff et al, PNAS 2011

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