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==== | ==Nanobody H3 AND C1 bound to RBD== | ||
<StructureSection load='7oap' size='340' side='right'caption='[[7oap]]' scene=''> | <StructureSection load='7oap' size='340' side='right'caption='[[7oap]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7oap]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama] 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=7OAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OAP FirstGlance]. <br> | ||
</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=7oap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oap OCA], [https://pdbe.org/7oap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oap RCSB], [https://www.ebi.ac.uk/pdbsum/7oap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oap ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.901Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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=7oap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oap OCA], [https://pdbe.org/7oap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oap RCSB], [https://www.ebi.ac.uk/pdbsum/7oap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oap ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered as homotrimers with pmolar affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Crystal structures show C5 and H3 overlap the ACE2 epitope, whilst C1 and F2 bind to a different epitope. Cryo Electron Microscopy shows C5 binding results in an all down arrangement of the Spike protein. C1, H3 and C5 all neutralize the Victoria strain, and the highly transmissible Alpha (B.1.1.7 first identified in Kent, UK) strain and C1 also neutralizes the Beta (B.1.35, first identified in South Africa). Administration of C5-trimer via the respiratory route showed potent therapeutic efficacy in the Syrian hamster model of COVID-19 and separately, effective prophylaxis. The molecule was similarly potent by intraperitoneal injection. | |||
A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19.,Huo J, Mikolajek H, Le Bas A, Clark JJ, Sharma P, Kipar A, Dormon J, Norman C, Weckener M, Clare DK, Harrison PJ, Tree JA, Buttigieg KR, Salguero FJ, Watson R, Knott D, Carnell O, Ngabo D, Elmore MJ, Fotheringham S, Harding A, Moynie L, Ward PN, Dumoux M, Prince T, Hall Y, Hiscox JA, Owen A, James W, Carroll MW, Stewart JP, Naismith JH, Owens RJ Nat Commun. 2021 Sep 22;12(1):5469. doi: 10.1038/s41467-021-25480-z. PMID:34552091<ref>PMID:34552091</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7oap" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Spike protein 3D structures|Spike protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: Mikolajek H]] | |||
[[Category: Naismith JH]] | |||
Latest revision as of 12:02, 17 October 2024
Nanobody H3 AND C1 bound to RBDNanobody H3 AND C1 bound to RBD
Structural highlights
Publication Abstract from PubMedSARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered as homotrimers with pmolar affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Crystal structures show C5 and H3 overlap the ACE2 epitope, whilst C1 and F2 bind to a different epitope. Cryo Electron Microscopy shows C5 binding results in an all down arrangement of the Spike protein. C1, H3 and C5 all neutralize the Victoria strain, and the highly transmissible Alpha (B.1.1.7 first identified in Kent, UK) strain and C1 also neutralizes the Beta (B.1.35, first identified in South Africa). Administration of C5-trimer via the respiratory route showed potent therapeutic efficacy in the Syrian hamster model of COVID-19 and separately, effective prophylaxis. The molecule was similarly potent by intraperitoneal injection. A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19.,Huo J, Mikolajek H, Le Bas A, Clark JJ, Sharma P, Kipar A, Dormon J, Norman C, Weckener M, Clare DK, Harrison PJ, Tree JA, Buttigieg KR, Salguero FJ, Watson R, Knott D, Carnell O, Ngabo D, Elmore MJ, Fotheringham S, Harding A, Moynie L, Ward PN, Dumoux M, Prince T, Hall Y, Hiscox JA, Owen A, James W, Carroll MW, Stewart JP, Naismith JH, Owens RJ Nat Commun. 2021 Sep 22;12(1):5469. doi: 10.1038/s41467-021-25480-z. PMID:34552091[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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