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	A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection.
Journal, issue, pages	Nat Commun, Vol. 12, Issue 1, Page 4635, Year 2021
Publish date	Jul 30, 2021
Authors	Tingting Li / Hongmin Cai / Hebang Yao / Bingjie Zhou / Ning Zhang / Martje Fentener van Vlissingen / Thijs Kuiken / Wenyu Han / Corine H GeurtsvanKessel / Yuhuan Gong / Yapei Zhao / Quan Shen / Wenming Qin / Xiao-Xu Tian / Chao Peng / Yanling Lai / Yanxing Wang / Cedric A J Hutter / Shu-Ming Kuo / Juan Bao / Caixuan Liu / Yifan Wang / Audrey S Richard / Hervé Raoul / Jiaming Lan / Markus A Seeger / Yao Cong / Barry Rockx / Gary Wong / Yuhai Bi / Dimitri Lavillette / Dianfan Li /
PubMed Abstract	SARS-CoV-2, the causative agent of COVID-19, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein. Neutralizing antibodies that block RBD-ACE2 interaction are candidates ...SARS-CoV-2, the causative agent of COVID-19, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein. Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic nanobodies (sybodies) against RBD by in vitro selection using three libraries. The best sybody, MR3 binds to RBD with high affinity (K = 1.0 nM) and displays high neutralization activity against SARS-CoV-2 pseudoviruses (IC = 0.42 μg mL). Structural, biochemical, and biological characterization suggests a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency have been generated by structure-based design, biparatopic construction, and divalent engineering. Two divalent forms of MR3 protect hamsters from clinical signs after live virus challenge and a single dose of the Fc-fusion construct of MR3 reduces viral RNA load by 6 Log. Our results pave the way for the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid development of targeted medical interventions during an outbreak.
External links	Nat Commun / PubMed:34330908 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.15 - 6.25 Å
Structure data	EMDB-31328: The cryo-EM map of the MR3-Spike complex Method: EM (single particle) / Resolution: 6.25 Å PDB-7c8v: Structure of sybody SR4 in complex with the SARS-CoV-2 S Receptor Binding domain (RBD) Method: X-RAY DIFFRACTION / Resolution: 2.15 Å PDB-7c8w: Structure of sybody MR17 in complex with the SARS-CoV-2 S receptor-binding domain (RBD) Method: X-RAY DIFFRACTION / Resolution: 2.77 Å PDB-7can: Structure of sybody MR17-K99Y in complex with the SARS-CoV-2 S Receptor-binding domain (RBD) Method: X-RAY DIFFRACTION / Resolution: 2.94 Å
Chemicals	ChemComp-GOL: GLYCEROL / Glycerol ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-HOH: WATER / Water
Source	severe acute respiratory syndrome coronavirus 2 synthetic construct (others)
Keywords	PROTEIN BINDING / coronavirus / Covid-19 / nanobody / neutralizing antibody / receptor binding protein / SARS-CoV-2 / S protein / synthetic antibody / VHH.