7p78 | pdb_00007p78

SARS-CoV-2 spike protein in complex with sybody#15 and sybody#68 in a 1up/1up-out/1down conformation

spinqualitylabelsall models 7p78, resolution 3.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7p78 is a 8 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.32Å Ligands: BMA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The ongoing COVID-19 pandemic represents an unprecedented global health crisis. Here, we report the identification of a synthetic nanobody (sybody) pair, Sb#15 and Sb#68, that can bind simultaneously to the SARS-CoV-2 spike RBD and efficiently neutralize pseudotyped and live viruses by interfering with ACE2 interaction. Cryo-EM confirms that Sb#15 and Sb#68 engage two spatially discrete epitopes, influencing rational design of bispecific and tri-bispecific fusion constructs that exhibit up to 100- and 1,000-fold increase in neutralization potency, respectively. Cryo-EM of the sybody-spike complex additionally reveals a novel up-out RBD conformation. While resistant viruses emerge rapidly in the presence of single binders, no escape variants are observed in the presence of the bispecific sybody. The multivalent bispecific constructs further increase the neutralization potency against globally circulating SARS-CoV-2 variants of concern. Our study illustrates the power of multivalency and biparatopic nanobody fusions for the potential development of therapeutic strategies that mitigate the emergence of new SARS-CoV-2 escape mutants. Biparatopic sybodies neutralize SARS-CoV-2 variants of concern and mitigate drug resistance.,Walter JD, Scherer M, Hutter CAJ, Garaeva AA, Zimmermann I, Wyss M, Rheinberger J, Ruedin Y, Earp JC, Egloff P, Sorgenfrei M, Hurlimann LM, Gonda I, Meier G, Remm S, Thavarasah S, van Geest G, Bruggmann R, Zimmer G, Slotboom DJ, Paulino C, Plattet P, Seeger MA EMBO Rep. 2022 Mar 7:e54199. doi: 10.15252/embr.202154199. PMID:35253970 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Spike protein 3D structures

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