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Viruses 2019, 11(2), 166; https://doi.org/10.3390/v11020166

Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain

1
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
2
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
3
Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 28 January 2019 / Revised: 14 February 2019 / Accepted: 15 February 2019 / Published: 19 February 2019
(This article belongs to the Special Issue MERS-CoV)
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Abstract

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), an infectious coronavirus first reported in 2012, has a mortality rate greater than 35%. Therapeutic antibodies are key tools for preventing and treating MERS-CoV infection, but to date no such agents have been approved for treatment of this virus. Nanobodies (Nbs) are camelid heavy chain variable domains with properties distinct from those of conventional antibodies and antibody fragments. We generated two oligomeric Nbs by linking two or three monomeric Nbs (Mono-Nbs) targeting the MERS-CoV receptor-binding domain (RBD), and compared their RBD-binding affinity, RBD–receptor binding inhibition, stability, and neutralizing and cross-neutralizing activity against MERS-CoV. Relative to Mono-Nb, dimeric Nb (Di-Nb) and trimeric Nb (Tri-Nb) had significantly greater ability to bind MERS-CoV RBD proteins with or without mutations in the RBD, thereby potently blocking RBD–MERS-CoV receptor binding. The engineered oligomeric Nbs were very stable under extreme conditions, including low or high pH, protease (pepsin), chaotropic denaturant (urea), and high temperature. Importantly, Di-Nb and Tri-Nb exerted significantly elevated broad-spectrum neutralizing activity against at least 19 human and camel MERS-CoV strains isolated in different countries and years. Overall, the engineered Nbs could be developed into effective therapeutic agents for prevention and treatment of MERS-CoV infection. View Full-Text
Keywords: Coronavirus; MERS-CoV; receptor-binding domain; therapeutic antibodies; nanobodies; cross-neutralization Coronavirus; MERS-CoV; receptor-binding domain; therapeutic antibodies; nanobodies; cross-neutralization
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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He, L.; Tai, W.; Li, J.; Chen, Y.; Gao, Y.; Li, J.; Sun, S.; Zhou, Y.; Du, L.; Zhao, G. Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain. Viruses 2019, 11, 166.

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