8dw2: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8dw2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_phage_EcSzw-2 Escherichia phage EcSzw-2], [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=8DW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DW2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8dw2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_phage_EcSzw-2 Escherichia phage EcSzw-2], [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=8DW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DW2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.11Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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=8dw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dw2 OCA], [https://pdbe.org/8dw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dw2 RCSB], [https://www.ebi.ac.uk/pdbsum/8dw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dw2 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=8dw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dw2 OCA], [https://pdbe.org/8dw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dw2 RCSB], [https://www.ebi.ac.uk/pdbsum/8dw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dw2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 13: | Line 14: | ||
We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective IC(50) values of 3.4, 2.2 and 7.4 ng ml(-1) for FSR16m. Cryo-EM structures revealed that these DARPins recognize a region of the receptor-binding domain (residues 456, 475, 486, 487 and 489) overlapping a critical portion of the angiotensin-converting enzyme 2 (ACE2)-binding surface. K18-hACE2 transgenic mice inoculated with B.1.617.2 and receiving intranasally administered FSR16m showed less weight loss and 10-100-fold lower viral burden in upper and lower respiratory tracts. The strong and broad neutralization potency makes FSR16m and FSR22 promising candidates for the prevention and treatment of infection by SARS-CoV-2. | We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective IC(50) values of 3.4, 2.2 and 7.4 ng ml(-1) for FSR16m. Cryo-EM structures revealed that these DARPins recognize a region of the receptor-binding domain (residues 456, 475, 486, 487 and 489) overlapping a critical portion of the angiotensin-converting enzyme 2 (ACE2)-binding surface. K18-hACE2 transgenic mice inoculated with B.1.617.2 and receiving intranasally administered FSR16m showed less weight loss and 10-100-fold lower viral burden in upper and lower respiratory tracts. The strong and broad neutralization potency makes FSR16m and FSR22 promising candidates for the prevention and treatment of infection by SARS-CoV-2. | ||
A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins.,Chonira V, Kwon YD, Gorman J, Case JB, Ku Z, Simeon R, Casner RG, Harris DR, Olia AS, Stephens T, Shapiro L, Bender MF, Boyd H, Teng IT, Tsybovsky Y, Krammer F, Zhang N, Diamond MS, Kwong PD, An Z, Chen Z Nat Chem Biol. | A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins.,Chonira V, Kwon YD, Gorman J, Case JB, Ku Z, Simeon R, Casner RG, Harris DR, Olia AS, Stephens T, Shapiro L, Bender MF, Boyd H, Teng IT, Tsybovsky Y, Krammer F, Zhang N, Diamond MS, Kwong PD, An Z, Chen Z Nat Chem Biol. 2023 Mar;19(3):284-291. doi: 10.1038/s41589-022-01193-2. Epub 2022 , Nov 21. PMID:36411391<ref>PMID:36411391</ref> | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 8dw2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8dw2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Spike protein 3D structures|Spike protein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||