8pq2 - Revision history

OCA at 09:03, 6 December 2023

OCA — Wed, 06 Dec 2023 09:03:22 GMT

←Older revision		Revision as of 09:03, 6 December 2023
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	</div>		</div>
	<div class="pdbe-citations 8pq2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 8pq2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Spike protein 3D structures\|Spike protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:11, 1 November 2023

OCA — Wed, 01 Nov 2023 13:11:11 GMT

←Older revision		Revision as of 13:11, 1 November 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8pq2 is ~~ON HOLD~~	+	==XBB 1.0 RBD bound to P4J15 (Local)==
		+	<StructureSection load='8pq2' size='340' side='right'caption='[[8pq2]], [[Resolution\|resolution]] 3.85Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8pq2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=8PQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PQ2 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]] 3.85Å</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=8pq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pq2 OCA], [https://pdbe.org/8pq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pq2 RCSB], [https://www.ebi.ac.uk/pdbsum/8pq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pq2 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 ==
		+	OBJECTIVES: Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection to immunocompromised patient populations. METHODS: Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 antibody was further characterized to define the structural binding epitope, viral resistance, and in vivo efficacy. RESULTS: The P4J15 mAb shows <20 ng/ml neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares approximately 93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. In vitro selection of SARS-CoV-2 mutants escaping P4J15 neutralization showed reduced infectivity, poor ACE2 binding, and mutations are rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, P4J15-LS confers complete prophylactic protection with an exceptionally long in vivo half-life of 43 days. CONCLUSIONS: The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations.

-	~~Authors: Duhoo~~, Y., Lau, K.	+	Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys.,Fenwick C, Turelli P, Duhoo Y, Lau K, Herate C, Marlin R, Lamrayah M, Campos J, Esteves-Leuenberger L, Farina A, Raclot C, Genet V, Fiscalini F, Cesborn J, Perez L, Dereuddre-Bosquet N, Contreras V, Lheureux K, Relouzat F, Abdelnabi R, Leyssen P, Levy Y, Pojer F, Stahlberg H, Le Grand R, Trono D, Pantaleo G J Infect. 2023 Oct 16:S0163-4453(23)00539-X. doi: 10.1016/j.jinf.2023.10.008. PMID:37852477<ref>PMID:37852477</ref>

-	~~Description: Potent Neutralizing Antibody with ACE2 mimetic properties provides full protection to SARS~~-~~CoV~~-~~2 XBB 1.0 RBD bound to P4J15 (Local)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Duhoo, Y]]	+	<div class="pdbe-citations 8pq2" style="background-color:#fffaf0;"></div>
-	[[Category: Lau, K]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Duhoo Y]]
		+	[[Category: Lau K]]

OCA at 05:49, 25 October 2023

OCA — Wed, 25 Oct 2023 05:49:28 GMT

←Older revision		Revision as of 05:49, 25 October 2023
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	Authors: Duhoo, Y., Lau, K.		Authors: Duhoo, Y., Lau, K.

-	Description: Potent Neutralizing Antibody with ACE2 mimetic properties provides full protection to SARS-CoV-2 XBB.1.~~5 challenged monkeys~~	+	Description: Potent Neutralizing Antibody with ACE2 mimetic properties provides full protection to SARS-CoV-2 XBB 1.0 RBD bound to P4J15 (Local)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Duhoo, Y]]		[[Category: Duhoo, Y]]
	[[Category: Lau, K]]		[[Category: Lau, K]]

OCA at 12:04, 18 October 2023

OCA — Wed, 18 Oct 2023 12:04:18 GMT

←Older revision		Revision as of 12:04, 18 October 2023
Line 5:		Line 5:
	Authors: Duhoo, Y., Lau, K.		Authors: Duhoo, Y., Lau, K.

-	Description: XBB 1.~~0 RBD bound to P4J15 (Local)~~	+	Description: Potent Neutralizing Antibody with ACE2 mimetic properties provides full protection to SARS-CoV-2 XBB.1.5 challenged monkeys
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Duhoo, Y]]		[[Category: Duhoo, Y]]
	[[Category: Lau, K]]		[[Category: Lau, K]]

OCA at 10:45, 4 October 2023

OCA — Wed, 04 Oct 2023 10:45:55 GMT

←Older revision		Revision as of 10:45, 4 October 2023
Line 5:		Line 5:
	Authors: Duhoo, Y., Lau, K.		Authors: Duhoo, Y., Lau, K.

-	Description: ~~Potent Neutralizing Antibody with ACE2 mimetic properties provides full protection to SARS-CoV-2~~ XBB.1.~~5 challenged monkeys~~	+	Description: XBB 1.0 RBD bound to P4J15 (Local)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Duhoo, Y]]		[[Category: Duhoo, Y]]
	[[Category: Lau, K]]		[[Category: Lau, K]]

OCA: Protected "8pq2" [edit=sysop:move=sysop]

OCA — Wed, 19 Jul 2023 04:53:36 GMT

Protected "8pq2" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:53, 19 July 2023

OCA: New page: '''Unreleased structure''' The entry 8pq2 is ON HOLD Authors: Duhoo, Y., Lau, K. Description: Potent Neutralizing Antibody with ACE2 mimetic properties provides full protection to SARS...

OCA — Wed, 19 Jul 2023 04:53:35 GMT

New page: '''Unreleased structure''' The entry 8pq2 is ON HOLD Authors: Duhoo, Y., Lau, K. Description: Potent Neutralizing Antibody with ACE2 mimetic properties provides full protection to SARS...

New page

'''Unreleased structure'''

The entry 8pq2 is ON HOLD

Authors: Duhoo, Y., Lau, K.

Description: Potent Neutralizing Antibody with ACE2 mimetic properties provides full protection to SARS-CoV-2 XBB.1.5 challenged monkeys
[[Category: Unreleased Structures]]
[[Category: Duhoo, Y]]
[[Category: Lau, K]]