Scientists funded in part by the March of Dimes have identified a “weak spot” in one of the Zika virus proteins that could provide a target for new drugs to fight the disease.
Jikui Song, Ph.D., an assistant professor of biochemistry at the University of California, Riverside, and his team studied the structure and function of the Zika protein NS5 (non-structural protein 5), one of just 10 proteins that make up the Zika virus particle. The NS5 protein is crucial to the life cycle of Zika, helping the virus replicate itself. NS5 also participates in helping the virus evade the host immune system.
In an article published in Nature Communications on March 27, Dr. Song and colleagues described the 3D structure of the entire NS5 protein and provide new insight into how it functions. They identified a potential binding site in the protein for an inhibitor, which could make possible the development of the first drugs to suppress Zika infection.
“This is an important finding that could be a first step toward treating Zika virus, an infection that is very dangerous to pregnant women and babies, and for which we currently have no treatment or vaccine,” says Joe Leigh Simpson, MD, senior vice president for Research and Global Programs at the March of Dimes.
Zika virus infection during pregnancy can cause damage to the brain, microcephaly (smaller than expected head) and congenital Zika syndrome, a pattern of conditions in the baby that includes brain abnormalities, eye defects, hearing loss, and limb defects. Zika infection during pregnancy also has been linked to miscarriage and stillbirth. A report from the U.S. Zika Pregnancy Registry on April 4 showed that among pregnant women with confirmed Zika infection in 2016, 10 percent had a fetus or baby with birth defects.
Dr. Song says the next step for the team is to investigate the antiviral potential against Zika of a chemical compound that previously has been shown to work against dengue virus, a close relative of Zika.
“The structure of Zika virus NS5 reveals a conserved domain conformation,” by Boxiao Wang et al. appears in Nature Communications 2017 Mar 27;8:14763, and was supported by grants from the March of Dimes, the Sidney Kimmel Foundation for Cancer Research and the National Institutes of Health.