| Literature DB >> 32661423 |
Jiandong Huo1,2,3, Audrey Le Bas2,3, Reinis R Ruza2, Helen M E Duyvesteyn2, Halina Mikolajek4, Tomas Malinauskas2, Tiong Kit Tan5, Pramila Rijal5,6, Maud Dumoux1, Philip N Ward2,3, Jingshan Ren2, Daming Zhou2, Peter J Harrison2,3, Miriam Weckener1, Daniel K Clare4, Vinod K Vogirala4, Julika Radecke4, Lucile Moynié1, Yuguang Zhao2, Javier Gilbert-Jaramillo7, Michael L Knight7, Julia A Tree8, Karen R Buttigieg8, Naomi Coombes8, Michael J Elmore8, Miles W Carroll8, Loic Carrique2, Pranav N M Shah2, William James7, Alain R Townsend5,6, David I Stuart2,4, Raymond J Owens9,10,11, James H Naismith12,13,14.
Abstract
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.Entities:
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Year: 2020 PMID： 32661423 DOI： 10.1038/s41594-020-0469-6
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN： 1545-9985 Impact factor: 15.369