NCI Researchers Discover Exceptionally Potent Antibodies with Potential for Prophylaxis and Therapy of MERS-Coronavirus Infections

Crystal structures.

Docked complexes of MERS-CoV RBD with mAbs (A) m336, (B) m337, and (C) m338. (D) Superposition of the docked complexes of RBD-m336,7,8 and the crystal structure of the RBD-DPP4 complex.

By Andrea Frydl, Contributing Writer

In a recent article published in the Journal of Virology, Tianlei Ying, Ph.D., Dimiter Dimitrov, Ph.D., and their colleagues in the Laboratory of Experimental Immunology (LEI), Cancer and Inflammation Program, NCI Center for Cancer Research, reported the identification of three human monoclonal antibodies (m336, m337, and m338) that target the part of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) that is responsible for binding to its receptor. These antibodies are exceptionally potent inhibitors of MERS-CoV infection and also provide a basis for creating a future MERS-CoV vaccine.

This work, a collaboration between LEI researchers Dimitrov, Ying, Ponraj Prabakaran, Yang Feng, Yanping Wang, and Tina Ju (a student intern) and Kwok Yuen (University of Hong Kong), Shibo Jiang (Fudan University, Shanghai, China), and their associates, achieved highly significant results, which may serve as the basis for the first therapeutic against the MERS-CoV.

The MERS-CoV is a lethal virus that was first found in the Middle East and for which there is no therapeutic to prevent its spread.  In its Morbidity and Mortality Weekly Report, dated May 16, 2014, the Centers for Disease Control and Prevention describe the first confirmed cases of MERS in the United States and the threat of MERS to public health.

Ying’s and Dimitrov’s research provides the first step toward identifying a therapeutic for the lethal virus, and, ideally, curing it. The process detailed in their paper also lends a basis for how to respond to other emerging coronaviruses.

Dimitrov said that an amazing aspect of this scientific finding is the speed with which the antibodies were discovered and their exceptional potency in combating the MERS-CoV.  “Dr. Tianlei Ying in our group made one of the world’s largest antibody libraries in less than two months and identified the antibodies within just a few weeks,” he explained. “The new antibodies are extremely potent and may save human lives and help prevent further spread of the MERS virus. Dr. Ying’s antibody library opens the door for a quick response to other emerging viruses, not just the MERS-CoV.”

Docked complexes of MERS-CoV RBD with mAbs (A) m336, (B) m337, and (C) m338. (D) Superposition of the docked complexes of RBD-m336,7,8 and the crystal structure of the RBD-DPP4 complex.

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