8el2: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==SARS-CoV-2 RBD bound to neutralizing antibody Fab ICO-hu23== | |||
<StructureSection load='8el2' size='340' side='right'caption='[[8el2]], [[Resolution|resolution]] 2.89Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8el2]] is a 6 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=8EL2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EL2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8el2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8el2 OCA], [https://pdbe.org/8el2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8el2 RCSB], [https://www.ebi.ac.uk/pdbsum/8el2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8el2 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses. | |||
Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates.,Hermet P, Delache B, Herate C, Wolf E, Kivi G, Juronen E, Mumm K, Zusinaite E, Kainov D, Sankovski E, Virumae K, Planken A, Merits A, Besaw JE, Yee AW, Morizumi T, Kim K, Kuo A, Berriche A, Dereuddre-Bosquet N, Sconosciuti Q, Naninck T, Relouzat F, Cavarelli M, Ustav M, Wilson D, Ernst OP, Mannik A, LeGrand R, Ustav M Jr PLoS Pathog. 2023 Aug 2;19(8):e1011532. doi: 10.1371/journal.ppat.1011532. , eCollection 2023 Aug. PMID:37531329<ref>PMID:37531329</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8el2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Spike protein 3D structures|Spike protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Besaw JE]] | |||
[[Category: Ernst OP]] | |||
[[Category: Kuo A]] | |||
[[Category: Morizumi T]] | |||