8Q7S

Crystal structure of the SARS-CoV-2 RBD (Wuhan) with neutralizing VHHs Ma6F06 and Re21H01

Summary for 8Q7S

• Entry DOI: 10.2210/pdb8q7s/pdb
• Descriptor: Spike protein S1, VHH Antibody Re21H01, VHH Antibody Ma6F06, ... (7 entities in total)
• Functional Keywords: sars-cov-2, vhh antibody, nanobody, antiviral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 15
• Total formula weight: 242450.91

Authors

Guttler, T.,Aksu, M.,Gorlich, D. (deposition date: 2023-08-16, release date: 2023-12-20, Last modification date: 2024-11-20)

Primary citation

Aksu, M.,Kumar, P.,Guttler, T.,Taxer, W.,Gregor, K.,Mussil, B.,Rymarenko, O.,Stegmann, K.M.,Dickmanns, A.,Gerber, S.,Reineking, W.,Schulz, C.,Henneck, T.,Mohamed, A.,Pohlmann, G.,Ramazanoglu, M.,Mese, K.,Gross, U.,Ben-Yedidia, T.,Ovadia, O.,Fischer, D.W.,Kamensky, M.,Reichman, A.,Baumgartner, W.,von Kockritz-Blickwede, M.,Dobbelstein, M.,Gorlich, D.
Nanobodies to multiple spike variants and inhalation of nanobody-containing aerosols neutralize SARS-CoV-2 in cell culture and hamsters.
Antiviral Res., 221:105778-105778, 2023

PubMed Abstract: The ongoing threat of COVID-19 has highlighted the need for effective prophylaxis and convenient therapies, especially for outpatient settings. We have previously developed highly potent single-domain (VHH) antibodies, also known as nanobodies, that target the Receptor Binding Domain (RBD) of the SARS-CoV-2 Spike protein and neutralize the Wuhan strain of the virus. In this study, we present a new generation of anti-RBD nanobodies with superior properties. The primary representative of this group, Re32D03, neutralizes Alpha to Delta as well as Omicron BA.2.75; other members neutralize, in addition, Omicron BA.1, BA.2, BA.4/5, and XBB.1. Crystal structures of RBD-nanobody complexes reveal how ACE2-binding is blocked and also explain the nanobodies' tolerance to immune escape mutations. Through the cryo-EM structure of the Ma16B06-BA.1 Spike complex, we demonstrated how a single nanobody molecule can neutralize a trimeric spike. We also describe a method for large-scale production of these nanobodies in Pichia pastoris, and for formulating them into aerosols. Exposing hamsters to these aerosols, before or even 24 h after infection with SARS-CoV-2, significantly reduced virus load, weight loss and pathogenicity. These results show the potential of aerosolized nanobodies for prophylaxis and therapy of coronavirus infections.

PubMed: 38065245
DOI: 10.1016/j.antiviral.2023.105778

Experimental method

X-RAY DIFFRACTION (2.7 Å)