Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain
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...
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MDPI AG
2019-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/11/2/166 |
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| author | Lei He Wanbo Tai Jiangfan Li Yuehong Chen Yaning Gao Junfeng Li Shihui Sun Yusen Zhou Lanying Du Guangyu Zhao |
| author_facet | Lei He Wanbo Tai Jiangfan Li Yuehong Chen Yaning Gao Junfeng Li Shihui Sun Yusen Zhou Lanying Du Guangyu Zhao |
| author_sort | Lei He |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T05:06:48Z |
| format | Article |
| id | doaj.art-9d267cb390864cd9a7295c150c54329a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-24T05:06:48Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-9d267cb390864cd9a7295c150c54329a2022-12-21T17:13:48ZengMDPI AGViruses1999-49152019-02-0111216610.3390/v11020166v11020166Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding DomainLei He0Wanbo Tai1Jiangfan Li2Yuehong Chen3Yaning Gao4Junfeng Li5Shihui Sun6Yusen Zhou7Lanying Du8Guangyu Zhao9State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaLindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USAState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaLindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USAState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaLindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USAState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaMiddle 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.https://www.mdpi.com/1999-4915/11/2/166CoronavirusMERS-CoVreceptor-binding domaintherapeutic antibodiesnanobodiescross-neutralization |
| spellingShingle | Lei He Wanbo Tai Jiangfan Li Yuehong Chen Yaning Gao Junfeng Li Shihui Sun Yusen Zhou Lanying Du Guangyu Zhao Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain Viruses Coronavirus MERS-CoV receptor-binding domain therapeutic antibodies nanobodies cross-neutralization |
| title | Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain |
| title_full | Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain |
| title_fullStr | Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain |
| title_full_unstemmed | Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain |
| title_short | Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain |
| title_sort | enhanced ability of oligomeric nanobodies targeting mers coronavirus receptor binding domain |
| topic | Coronavirus MERS-CoV receptor-binding domain therapeutic antibodies nanobodies cross-neutralization |
| url | https://www.mdpi.com/1999-4915/11/2/166 |
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