Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2
The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Usi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2020
|
| _version_ | 1826271256644681728 |
|---|---|
| author | Huo, J Le Bas, A Ruza, RR Duyvesten, HME Mikolajek, H Malinauskas, T Tan, TK Rijal, P Dumoux, M Ward, PN Ren, J Zhou, D Harrison, PJ Weckener, M Clare, DK Vogirala, VK Radecke, J Moynié, L Zhao, Y Gilbert-Jaramillo, J Knight, ML Tree, JA Buttigieg, KR Coombes, N Elmore, MJ Carroll, MW Carrique, L Shah, PNM James, W Townsend, AR Stuart, DI Owens, RJ Naismith, JH |
| author_facet | Huo, J Le Bas, A Ruza, RR Duyvesten, HME Mikolajek, H Malinauskas, T Tan, TK Rijal, P Dumoux, M Ward, PN Ren, J Zhou, D Harrison, PJ Weckener, M Clare, DK Vogirala, VK Radecke, J Moynié, L Zhao, Y Gilbert-Jaramillo, J Knight, ML Tree, JA Buttigieg, KR Coombes, N Elmore, MJ Carroll, MW Carrique, L Shah, PNM James, W Townsend, AR Stuart, DI Owens, RJ Naismith, JH |
| author_sort | Huo, J |
| collection | OXFORD |
| description | The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (KD of 39 and 12 nM, respectively) and block its interaction with ACE2. Single-particle cryo-EM revealed that both nanobodies bind to all three RBDs in the spike trimer. Crystal structures of each nanobody-RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD-ACE2 interaction. Nanobody-Fc fusions showed neutralizing activity against SARS-CoV-2 (4-6 nM for H11-H4, 18 nM for H11-D4) and additive neutralization with the SARS-CoV-1/2 antibody CR3022. |
| first_indexed | 2024-03-06T21:53:48Z |
| format | Journal article |
| id | oxford-uuid:4c358ed6-82bf-4e66-84d0-88ef9b53bf05 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:53:48Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:4c358ed6-82bf-4e66-84d0-88ef9b53bf052022-03-26T15:48:12ZNeutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4c358ed6-82bf-4e66-84d0-88ef9b53bf05EnglishSymplectic ElementsSpringer Nature 2020Huo, JLe Bas, ARuza, RRDuyvesten, HMEMikolajek, HMalinauskas, TTan, TKRijal, PDumoux, MWard, PNRen, JZhou, DHarrison, PJWeckener, MClare, DKVogirala, VKRadecke, JMoynié, LZhao, YGilbert-Jaramillo, JKnight, MLTree, JAButtigieg, KRCoombes, NElmore, MJCarroll, MWCarrique, LShah, PNMJames, WTownsend, ARStuart, DIOwens, RJNaismith, JHThe SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (KD of 39 and 12 nM, respectively) and block its interaction with ACE2. Single-particle cryo-EM revealed that both nanobodies bind to all three RBDs in the spike trimer. Crystal structures of each nanobody-RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD-ACE2 interaction. Nanobody-Fc fusions showed neutralizing activity against SARS-CoV-2 (4-6 nM for H11-H4, 18 nM for H11-D4) and additive neutralization with the SARS-CoV-1/2 antibody CR3022. |
| spellingShingle | Huo, J Le Bas, A Ruza, RR Duyvesten, HME Mikolajek, H Malinauskas, T Tan, TK Rijal, P Dumoux, M Ward, PN Ren, J Zhou, D Harrison, PJ Weckener, M Clare, DK Vogirala, VK Radecke, J Moynié, L Zhao, Y Gilbert-Jaramillo, J Knight, ML Tree, JA Buttigieg, KR Coombes, N Elmore, MJ Carroll, MW Carrique, L Shah, PNM James, W Townsend, AR Stuart, DI Owens, RJ Naismith, JH Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 |
| title | Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 |
| title_full | Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 |
| title_fullStr | Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 |
| title_full_unstemmed | Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 |
| title_short | Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 |
| title_sort | neutralizing nanobodies bind sars cov 2 spike rbd and block interaction with ace2 |
| work_keys_str_mv | AT huoj neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT lebasa neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT ruzarr neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT duyvestenhme neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT mikolajekh neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT malinauskast neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT tantk neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT rijalp neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT dumouxm neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT wardpn neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT renj neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT zhoud neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT harrisonpj neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT weckenerm neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT claredk neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT vogiralavk neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT radeckej neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT moyniel neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT zhaoy neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT gilbertjaramilloj neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT knightml neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT treeja neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT buttigiegkr neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT coombesn neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT elmoremj neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT carrollmw neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT carriquel neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT shahpnm neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT jamesw neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT townsendar neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT stuartdi neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT owensrj neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 AT naismithjh neutralizingnanobodiesbindsarscov2spikerbdandblockinteractionwithace2 |