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-Structure paper
タイトル | Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 27, Issue 9, Page 846-854, Year 2020 |
掲載日 | 2020年7月13日 |
著者 | Jiandong Huo / Audrey Le Bas / Reinis R Ruza / Helen M E Duyvesteyn / Halina Mikolajek / Tomas Malinauskas / Tiong Kit Tan / Pramila Rijal / Maud Dumoux / Philip N Ward / Jingshan Ren / Daming Zhou / Peter J Harrison / Miriam Weckener / Daniel K Clare / Vinod K Vogirala / Julika Radecke / Lucile Moynié / Yuguang Zhao / Javier Gilbert-Jaramillo / Michael L Knight / Julia A Tree / Karen R Buttigieg / Naomi Coombes / Michael J Elmore / Miles W Carroll / Loic Carrique / Pranav N M Shah / William James / Alain R Townsend / David I Stuart / Raymond J Owens / James H Naismith / |
PubMed 要旨 | 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 ...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 (K 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. |
リンク | Nat Struct Mol Biol / PubMed:32661423 |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.3 - 3.7 Å |
構造データ | EMDB-11068, PDB-6z43: EMDB-11218, PDB-6zhd: PDB-6zh9: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / Spike / nanobody / VHH / SARS-CoV-2 / COVID-19 / ANTIVIRAL PROTEIN / Covid19 / llama / neutralisation |