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Friday, March 5th, 2021

Researchers identify three-dimensional shapes of two enzymes needed for Zika virus replication

A research team at the Icahn School of Medicine at Mount Sinai recently published two studies that identify the three-dimensional shapes of two enzymes critical to replication and survival of the Zika virus.

The first study, published in Nature Structural & Molecular Biology, examined examined the enzyme NS3, which unwinds RNA and is responsible for the virus’ replication.

The second study, published in Cell Reports, analyzed the enzyme NS5, which is needed to cap the viral genome, which is needed for the creation of stable RNA for viral replication.

The researchers identified the shape of the enzymes in a short amount of time and made their results available to research teams across the world who are working to find effective treatments for the Zika virus. Drug development within the field of structural biology relies on high-resolution three-dimensional structures for study.

The studies were led by Dr. Aneel Aggarwal, professor of pharmacological sciences and oncological sciences at the Icahn School. Assisting in the study was Rinku Kain, assistant professor of pharmacological sciences, and Adolfo Garcia-Sartre, professor of microbiology and director of the Global Health and Emerging Pathogen Institute at the Icahn School of Medicine.

“The next step would be to develop compounds to inhibit these enzymes’ actions by physically blocking them, interfering with the reproduction of the virus,” Aggarwal said. “We are fortunate to be able to collaborate with some of the best computational and medicinal chemists and virologists right here at Mount Sinai.”

Zika virus is typically spread through the bite of Aedes mosquitoes and often shows no or only mild symptoms. When spread to pregnant women, however, the virus can cause birth defects such as microcephaly in the fetus. The virus has emerged as a major health concern as it continues to spread through South and Central America, as well as parts of North America. There is currently no treatment for Zika.