Mount Sinai Studies Inform Path to Zika Treatment
Researchers at the Icahn School of Medicine at Mount Sinai are working on the basic science that lays the groundwork to finding a way to treat and prevent the Zika virus, a global health risk. In two papers published this fall, one in the journal Nature Structural & Molecular Biology, and the other in the journal Cell Reports, researchers identified the three-dimensional shapes of two enzymes critical to replication and survival of the virus.
The first study looked at the enzyme NS3, which unwinds RNA and is essential for the virus’s replication. The second study examined the enzyme NS5, which is responsible for capping the viral genome, which is vital in the creation of stable RNA for viral replication. Both studies were performed by a team led by Aneel Aggarwal, PhD, Professor of Pharmacological Sciences and Oncological Sciences at the Icahn School of Medicine at Mount Sinai, and which also included Rinku Jain, PhD, Assistant Professor of Pharmacological Sciences, and Adolfo García-Sastre, PhD, Professor of Microbiology and Director of the Global Health & Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai, as well as their former colleague Javier Colomo, PhD.
“Determining the three-dimensional structures of a virus and its enzymes is a crucial prerequisite for structure-based drug discovery,” said Dr. Aggarwal. “Once we know the precise shape of these entities, we can work on inhibiting them.”
Drug development within the field of structural biology relies on high-resolution three-dimensional structures coupled with computational and medicinal chemistry. While the same enzymes exist in other flaviviruses (such as Dengue and West Nile), the exact shape of the enzymes is different in each virus. In these studies, Dr. Aggarwal and his team identified the shape of the enzymes in a short amount of time and immediately made their results available to researchers throughout the world working to find an effective treatment for Zika virus.
“The next step would be to develop compounds to inhibit these enzymes’ actions by physically blocking them, interfering with the reproduction of the virus,” said Dr. Aggarwal. “We are fortunate to be able to collaborate with some of the best computational and medicinal chemists and virologists right here at Mount Sinai.”
The Zika virus has emerged as a major health concern over the past year, spreading rapidly across parts of South and Central America, as well as some parts of North America. It has been linked to birth defects in newborn infants and Guillain-Barré syndrome in adults. At this point, there is no effective way of preventing infection once people are exposed to Zika-carrying mosquitoes.
“We hope this work will lead to the development of effective treatments that help alleviate the terrible effects of Zika, and we see ourselves as part of a world-wide effort,” said Dr. Aggarwal.
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.