By Henry Workman
Marine Science Today Writer
A virus-fighting substance known as squalamine is the subject of new research published in Proceedings of the National Academy of Sciences (PNAS). The compound was originally discovered in the liver of dogfish, where it plays an important role in protecting it, as well as some other species, from viral infections and tumor growth. The study indicates that squalamine can act against certain human viruses in a similar way. Whereas many pharmaceuticals currently on the market are rendered useless after viruses develop resistances to them, squalamine’s indicated mechanism of action allows for far less susceptibility to this persisting obstacle.
Squalamine may have given sharks an edge against a wide range of health threats in their 700-million-year history on Earth. Discovered in 1993 by Dr. Michael Zasloff (also the lead author of the new paper, now working at the Georgetown University Medical Center), the substance was studied as a broad-spectrum antibiotic, and for a period as a potential cancer treatment. Since that time clinical trials have been done on humans and a safety profile has been identified. Scientists have also successfully created quantities of squalamine in a laboratory setting, eliminating the need to harm threatened shark populations.
Though the squalamine molecule belongs to a class of similar compounds found in its origin species, it’s structurally distinct from any found in the human immune system. In sharks, it has been shown to inhibit the growth of new blood vessels in a tumor-preventing process known as anti-angiogenesis, which exists in various forms throughout the animal kingdom. Its anti-viral properties work by altering cells in the body to make them less receptive to viral replication. Squalamine enters through special channels and detaches proteins from the cell’s inner membrane. In doing so it removes an essential component from the invading viruses’ reproduction process, and does no damage to the cell.
The latest study tested whether squalamine could carry out this function in human cells and treat known human pathogens. It was introduced to both human tissue cultures and live animals infected with viruses such as yellow fever and hepatitis. The results clearly indicated an improvement in both, against a variety of threats. Some of the test animals recovered from their infection completely. This outcome will most likely lead to further investigations on squalamine as a new approach to curing diseases that would otherwise be diagnosed as chronic conditions.
The road to development of an approved squalamine-based pharmaceutical may be fraught with challenges, however. The level of toxicity outside of the organisms that naturally produce squalamine has been demonstrated to be significant, with problematic side-effects occurring at the doses required to fight viruses. There are also limitations on the types of tissue cells that squalamine can penetrate, rendering it useless against viruses in certain parts of the body. Despite this, it may be possible to engineer the structure of the molecule to make it better suited to the human body, resulting in a more specialized derivative.
Copyright © 2011 by Marine Science Today, a publication of OceanLines LLC.