New partnership investigates potential inhibitors of furin, a protein vital to the lifecycle of dengue fever virus and other infectious tropical diseases.
Sanford-Burnham Medical Research Institute (Sanford-Burnham) and 60- Pharmaceuticals, LLC, have entered into a partnership to test furin, a human proteinase, as a drug target for the treatment of dengue fever, one of the most common infectious diseases in the tropics and subtropics. 60- Pharmaceuticals, a philanthropic-for-profit company focused on neglected and rare diseases, agreed to provide funding to Sanford-Burnham for the first phase of research to explore inhibitors of furin.
Since viral genomes are too small to encode every protein needed for their survival, they take advantage of proteins in their human hosts. For the dengue virus and numerous other viruses-such as West Nile, Ebola, or yellow fever-furin is a vital host protein. For this reason, these viruses can only attack human cells that produce furin. Scientists at Sanford-Burnham are now trying to find a way to inhibit furin, making it impossible for the dengue virus to exploit and "hijack" a host cell.
"We're working on a new small-molecule furin inhibitor. It's a challenge to design, but could solve the toxicity problem that plagues existing viral inhibitors," explains Alex Strongin, Ph.D., professor in Sanford-Burnham's Infectious and Inflammatory Disease Center.
During the first phase of the research partnership, Drs. Alex Strongin and Maurizio Pellecchia and their laboratories at Sanford-Burnham will identify the most promising lead candidate from multiple small-molecule compounds they have already synthesized and tested in cell-based tests. They will evaluate each compound's absorption and distribution in the body (pharmacokinetics), as well as toxicity and efficacy in animal models. These data will inform potential second-phase research, which will focus on further developing the lead compound for oral application.
"The partnership with Sanford-Burnham exemplifies our commitment to developing treatments for the world's most challenging and neglected diseases, such as dengue fever," adds Geoffrey Dow, CEO of 60- Pharmaceuticals. "Only a combined effort can help address these challenges and make a real difference in the lives of millions of people living in regions affected by the dengue virus. Our goal is to find a treatment that is affordable, safe in warm and humid climates, and easy to administer."
Successfully designing a small-molecule inhibitor of furin that is safe and effective could have implications far beyond dengue fever. Given the protein's prevalence and important role in the lifecycle of a variety of viruses, a potent inhibitor could eventually lead to treatment options for many more viral diseases, affecting hundreds of millions of people worldwide.
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