7qtk: Difference between revisions
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qtk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qtk OCA], [https://pdbe.org/7qtk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qtk RCSB], [https://www.ebi.ac.uk/pdbsum/7qtk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qtk ProSAT]</span></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=7qtk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qtk OCA], [https://pdbe.org/7qtk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qtk RCSB], [https://www.ebi.ac.uk/pdbsum/7qtk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qtk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The SARS-CoV-2 Omicron variant has very high levels of transmission, is resistant to neutralization by authorized therapeutic human monoclonal antibodies (mAb) and is less sensitive to vaccine-mediated immunity. To provide additional therapies against Omicron, we isolated a mAb named P2G3 from a previously infected vaccinated donor and showed that it has picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other variants tested. We solved the structure of P2G3 Fab in complex with the Omicron spike using cryo-electron microscopy at 3.04 A resolution to identify the P2G3 epitope as a Class 3 mAb that is different from mAb-binding spike epitopes reported previously. Using a SARS-CoV-2 Omicron monkey challenge model, we show that P2G3 alone, or in combination with P5C3 (a broadly active Class 1 mAb previously identified), confers complete prophylactic or therapeutic protection. Although we could select for SARS-CoV-2 mutants escaping neutralization by P2G3 or by P5C3 in vitro, they had low infectivity and 'escape' mutations are extremely rare in public sequence databases. We conclude that this combination of mAbs has potential as an anti-Omicron drug. | |||
Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys.,Fenwick C, Turelli P, Ni D, Perez L, Lau K, Herate C, Marlin R, Lana E, Pellaton C, Raclot C, Esteves-Leuenberger L, Campos J, Farina A, Fiscalini F, Dereuddre-Bosquet N, Relouzat F, Abdelnabi R, Foo CS, Neyts J, Leyssen P, Levy Y, Pojer F, Stahlberg H, LeGrand R, Trono D, Pantaleo G Nat Microbiol. 2022 Sep;7(9):1376-1389. doi: 10.1038/s41564-022-01198-6. Epub, 2022 Jul 25. PMID:35879526<ref>PMID:35879526</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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<div class="pdbe-citations 7qtk" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 21:57, 7 September 2022
SARS-CoV-2 S Omicron Spike B.1.1.529 - RBD down - 1-P2G3 Fab (Local)SARS-CoV-2 S Omicron Spike B.1.1.529 - RBD down - 1-P2G3 Fab (Local)
Structural highlights
Publication Abstract from PubMedThe SARS-CoV-2 Omicron variant has very high levels of transmission, is resistant to neutralization by authorized therapeutic human monoclonal antibodies (mAb) and is less sensitive to vaccine-mediated immunity. To provide additional therapies against Omicron, we isolated a mAb named P2G3 from a previously infected vaccinated donor and showed that it has picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other variants tested. We solved the structure of P2G3 Fab in complex with the Omicron spike using cryo-electron microscopy at 3.04 A resolution to identify the P2G3 epitope as a Class 3 mAb that is different from mAb-binding spike epitopes reported previously. Using a SARS-CoV-2 Omicron monkey challenge model, we show that P2G3 alone, or in combination with P5C3 (a broadly active Class 1 mAb previously identified), confers complete prophylactic or therapeutic protection. Although we could select for SARS-CoV-2 mutants escaping neutralization by P2G3 or by P5C3 in vitro, they had low infectivity and 'escape' mutations are extremely rare in public sequence databases. We conclude that this combination of mAbs has potential as an anti-Omicron drug. Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys.,Fenwick C, Turelli P, Ni D, Perez L, Lau K, Herate C, Marlin R, Lana E, Pellaton C, Raclot C, Esteves-Leuenberger L, Campos J, Farina A, Fiscalini F, Dereuddre-Bosquet N, Relouzat F, Abdelnabi R, Foo CS, Neyts J, Leyssen P, Levy Y, Pojer F, Stahlberg H, LeGrand R, Trono D, Pantaleo G Nat Microbiol. 2022 Sep;7(9):1376-1389. doi: 10.1038/s41564-022-01198-6. Epub, 2022 Jul 25. PMID:35879526[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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