We’re partnering with 60° Pharmaceuticals 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, will provide funding for the first phase of our 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 in our Infectious and Inflammatory Disease Center 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 our Infectious and Inflammatory Disease Center.
During the first phase of the research partnership, Strongin, Maurizio Pellecchia, Ph.D., and their laboratories will identify the most promising lead candidate from multiple small-molecule compounds they have already synthesized and tested in cell-based experiments. 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.
About Dengue Fever
Dengue fever is an infectious tropical disease caused by the dengue virus, which is transmitted by mosquitoes. According to the Centers for Disease Control and Prevention, more than one-third of the world’s population is living in areas at risk for transmission of the virus. Dengue infection is a leading cause of illness and death in the tropics and subtropics and as many as 100 million people are infected every year. There are currently no vaccines to prevent infection with the virus and the most effective protective measures so far have been those that protect from mosquito bites. Data on the global economic impact of dengue fever are not available, but according to a 2012 study by 60° Pharmaceuticals, the global economic burden of dengue fever is at least $1.7 billion per year.