Details

Autor(en) / Beteiligte

• Huo, Jiandong
• Le Bas, Audrey
• Ruza, Reinis R
• Duyvesteyn, Helen M E
• Mikolajek, Halina
• Malinauskas, Tomas
• Tan, Tiong Kit
• Rijal, Pramila
• Dumoux, Maud
• Ward, Philip N
• Ren, Jingshan
• Zhou, Daming
• Harrison, Peter J
• Weckener, Miriam
• Clare, Daniel K
• Vogirala, Vinod K
• Radecke, Julika
• Moynié, Lucile
• Zhao, Yuguang
• Gilbert-Jaramillo, Javier
• Knight, Michael L
• Tree, Julia A
• Buttigieg, Karen R
• Coombes, Naomi
• Elmore, Michael J
• Carroll, Miles W
• Carrique, Loic
• Shah, Pranav N M
• James, William
• Townsend, Alain R
• Stuart, David I
• Owens, Raymond J
• Naismith, James H

Titel

Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2

Ist Teil von

• Nature structural & molecular biology, 2020-09, Vol.27 (9), p.846-854

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.