Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Nanobodies to multiple spike variants and inhalation of nanobody-containing aerosols neutralize SARS-CoV-2 in cell culture and hamsters.
Journal, issue, pages	Antiviral Res, Vol. 221, Page 105778, Year 2024
Publish date	Dec 7, 2023
Authors	Metin Aksu / Priya Kumar / Thomas Güttler / Waltraud Taxer / Kathrin Gregor / Bianka Mußil / Oleh Rymarenko / Kim M Stegmann / Antje Dickmanns / Sabrina Gerber / Wencke Reineking / Claudia Schulz / Timo Henneck / Ahmed Mohamed / Gerhard Pohlmann / Mehmet Ramazanoglu / Kemal Mese / Uwe Groß / Tamar Ben-Yedidia / Oded Ovadia / Dalit Weinstein Fischer / Merav Kamensky / Amir Reichman / Wolfgang Baumgärtner / Maren von Köckritz-Blickwede / Matthias Dobbelstein / Dirk Görlich /
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- ...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.
External links	Antiviral Res / PubMed:38065245
Methods	EM (single particle) / X-ray diffraction
Resolution	1.6 - 3.6 Å
Structure data	EMDB-18941: SARS-CoV-2 S (Spike) protein (BA.1) in complex with VHH Ma16B06 (sub-volume of two adjacent RBD-VHH modules) Method: EM (single particle) / Resolution: 3.6 Å PDB-8q7s: Crystal structure of the SARS-CoV-2 RBD (Wuhan) with neutralizing VHHs Ma6F06 and Re21H01 Method: X-RAY DIFFRACTION / Resolution: 2.7 Å PDB-8q93: Crystal structure of the SARS-COV-2 RBD with neutralizing-VHHs Re30H02 and Re21D01 Method: X-RAY DIFFRACTION / Resolution: 3.1 Å PDB-8q94: Crystal structure of The SARS-COV-2 BA.2.75 RBD with neutralizing-VHHs Re32D03 and Ma3B12 Method: X-RAY DIFFRACTION / Resolution: 2.5 Å PDB-8q95: Crystal structure of the SARS-CoV-2 BA.1 RBD with neutralizing-VHHs Ma16B06 and Ma3F05 Method: X-RAY DIFFRACTION / Resolution: 1.6 Å
Chemicals	ChemComp-P4G: 1-ETHOXY-2-(2-ETHOXYETHOXY)ETHANE ChemComp-EDO: 1,2-ETHANEDIOL ChemComp-GOL: GLYCEROL ChemComp-HOH: WATER
Source	Severe acute respiratory syndrome coronavirus vicugna pacos (alpaca) severe acute respiratory syndrome coronavirus 2
Keywords	ANTIVIRAL PROTEIN / SARS-CoV-2 / VHH Antibody / Nanobody / VIRAL PROTEIN / Neutralizing VHH / Fold-promoter