7nt4
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 1: | Line 1: | ||
==X-ray structure of SCoV2-PLpro in complex with small molecule inhibitor== | ==X-ray structure of SCoV2-PLpro in complex with small molecule inhibitor== | ||
| - | <StructureSection load='7nt4' size='340' side='right'caption='[[7nt4]]' scene=''> | + | <StructureSection load='7nt4' size='340' side='right'caption='[[7nt4]], [[Resolution|resolution]] 2.68Å' 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=7NT4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NT4 FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NT4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NT4 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=7nt4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nt4 OCA], [https://pdbe.org/7nt4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nt4 RCSB], [https://www.ebi.ac.uk/pdbsum/7nt4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nt4 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]] 2.68Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PRL:PROFLAVIN'>PRL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7nt4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nt4 OCA], [https://pdbe.org/7nt4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nt4 RCSB], [https://www.ebi.ac.uk/pdbsum/7nt4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nt4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PL(pro)) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PL(pro) catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks. | ||
| + | |||
| + | Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses.,Napolitano V, Dabrowska A, Schorpp K, Mourao A, Barreto-Duran E, Benedyk M, Botwina P, Brandner S, Bostock M, Chykunova Y, Czarna A, Dubin G, Frohlich T, Holscher M, Jedrysik M, Matsuda A, Owczarek K, Pachota M, Plettenburg O, Potempa J, Rothenaigner I, Schlauderer F, Slysz K, Szczepanski A, Greve-Isdahl Mohn K, Blomberg B, Sattler M, Hadian K, Popowicz GM, Pyrc K Cell Chem Biol. 2022 Jan 11. pii: S2451-9456(21)00513-4. doi:, 10.1016/j.chembiol.2021.11.006. PMID:35021060<ref>PMID:35021060</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7nt4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
X-ray structure of SCoV2-PLpro in complex with small molecule inhibitor
| |||||||||||
