7yvg: Difference between revisions

Latest revision as of 06:37, 3 July 2025

Omicron BA.4/5 SARS-CoV-2 S in complex with TH132 Fab

Structural highlights

7yvg is a 9 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.4Å
Ligands:	NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2-5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT(50) values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.

Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.,Guo Y, Zhang G, Yang Q, Xie X, Lu Y, Cheng X, Wang H, Liang J, Tang J, Gao Y, Shang H, Dai J, Shi Y, Zhou J, Zhou J, Guo H, Yang H, Qi J, Liu L, Ma S, Zhang B, Huo Q, Xie Y, Wu J, Dong F, Zhang S, Lou Z, Gao Y, Song Z, Wang W, Sun Z, Yang X, Xiong D, Liu F, Chen X, Zhu P, Wang X, Cheng T, Rao Z Nat Commun. 2023 Jun 15;14(1):3537. doi: 10.1038/s41467-023-39267-x. PMID:37322000^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Guo Y, Zhang G, Yang Q, Xie X, Lu Y, Cheng X, Wang H, Liang J, Tang J, Gao Y, Shang H, Dai J, Shi Y, Zhou J, Zhou J, Guo H, Yang H, Qi J, Liu L, Ma S, Zhang B, Huo Q, Xie Y, Wu J, Dong F, Zhang S, Lou Z, Gao Y, Song Z, Wang W, Sun Z, Yang X, Xiong D, Liu F, Chen X, Zhu P, Wang X, Cheng T, Rao Z. Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection. Nat Commun. 2023 Jun 15;14(1):3537. PMID:37322000 doi:10.1038/s41467-023-39267-x

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Guo Y, Zhang G, Yang Q, Xie X, Lu Y, Cheng X, Wang H, Liang J, Tang J, Gao Y, Shang H, Dai J, Shi Y, Zhou J, Zhou J, Guo H, Yang H, Qi J, Liu L, Ma S, Zhang B, Huo Q, Xie Y, Wu J, Dong F, Zhang S, Lou Z, Gao Y, Song Z, Wang W, Sun Z, Yang X, Xiong D, Liu F, Chen X, Zhu P, Wang X, Cheng T, Rao Z. Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection. Nat Commun. 2023 Jun 15;14(1):3537. PMID:37322000 doi:10.1038/s41467-023-39267-x

[1]

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7yvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yvg OCA], [https://pdbe.org/7yvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yvg RCSB], [https://www.ebi.ac.uk/pdbsum/7yvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yvg ProSAT]</span></td></tr>
 </table>
-== Function ==
-[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</ref>   mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099]  Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

7yvg: Difference between revisions

Latest revision as of 06:37, 3 July 2025

Omicron BA.4/5 SARS-CoV-2 S in complex with TH132 Fab

Structural highlights

Publication Abstract from PubMed

References

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