7xrp: Difference between revisions
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The | ==Cryo-EM structure of SARS-CoV-2 spike protein in complex with nanobody C5G2 (localized refinement)== | ||
<StructureSection load='7xrp' size='340' side='right'caption='[[7xrp]], [[Resolution|resolution]] 3.88Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7xrp]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelus_dromedarius Camelus dromedarius] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XRP FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.88Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7xrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xrp OCA], [https://pdbe.org/7xrp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xrp RCSB], [https://www.ebi.ac.uk/pdbsum/7xrp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xrp ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to the RBD domain and inhibits its binding to ACE2 with an IC(50) of 3.7 nM. Pseudovirus assays indicated that monovalent C5G2 could protect the cells from infection with SARS-CoV-2 wild-type virus and most of the viruses of concern, i.e., Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron BA.1 among all the variants, with an IC(50) of 4.9 ng/mL. The cryo-EM structure of C5G2 in complex with the spike trimer showed that C5G2 binds to RBD mainly through its CDR3 at a conserved region that does not overlap with the ACE2 binding surface. Additionally, C5G2 binds simultaneously to the neighboring NTD domain of the spike trimer through the same CDR3 loop, which may further increase its potency against viral infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may serve as an effective drug for prophylaxis and therapy against Omicron as well as future variants. | |||
A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode.,Zhao D, Liu L, Liu X, Zhang J, Yin Y, Luan L, Jiang D, Yang X, Li L, Xiong H, Xing D, Zheng Q, Xia N, Tao Y, Li S, Huang H J Nanobiotechnology. 2022 Sep 15;20(1):411. doi: 10.1186/s12951-022-01619-y. PMID:36109732<ref>PMID:36109732</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7xrp" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Liu | ==See Also== | ||
[[Category: | *[[Spike protein 3D structures|Spike protein 3D structures]] | ||
[[Category: Sun | == References == | ||
[[Category: Xia | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Camelus dromedarius]] | |||
[[Category: Large Structures]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Jiang Y]] | |||
[[Category: Li S]] | |||
[[Category: Liu L]] | |||
[[Category: Liu X]] | |||
[[Category: Sun H]] | |||
[[Category: Xia N]] | |||
[[Category: Zhao D]] | |||
[[Category: Zheng Q]] | |||
Latest revision as of 12:21, 17 October 2024
Cryo-EM structure of SARS-CoV-2 spike protein in complex with nanobody C5G2 (localized refinement)Cryo-EM structure of SARS-CoV-2 spike protein in complex with nanobody C5G2 (localized refinement)
Structural highlights
Publication Abstract from PubMedThe major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to the RBD domain and inhibits its binding to ACE2 with an IC(50) of 3.7 nM. Pseudovirus assays indicated that monovalent C5G2 could protect the cells from infection with SARS-CoV-2 wild-type virus and most of the viruses of concern, i.e., Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron BA.1 among all the variants, with an IC(50) of 4.9 ng/mL. The cryo-EM structure of C5G2 in complex with the spike trimer showed that C5G2 binds to RBD mainly through its CDR3 at a conserved region that does not overlap with the ACE2 binding surface. Additionally, C5G2 binds simultaneously to the neighboring NTD domain of the spike trimer through the same CDR3 loop, which may further increase its potency against viral infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may serve as an effective drug for prophylaxis and therapy against Omicron as well as future variants. A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode.,Zhao D, Liu L, Liu X, Zhang J, Yin Y, Luan L, Jiang D, Yang X, Li L, Xiong H, Xing D, Zheng Q, Xia N, Tao Y, Li S, Huang H J Nanobiotechnology. 2022 Sep 15;20(1):411. doi: 10.1186/s12951-022-01619-y. PMID:36109732[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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