8fiv: Difference between revisions

(One intermediate revision by the same user not shown)

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 8fiv is ~~ON HOLD until Paper~~ Publication

==Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor Jun10541R==

== Structural highlights ==

<table><tr><td colspan='2'>[[8fiv]] is a 1 chain structure with sequence from [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=8FIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FIV 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]] 2.51Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y0I:(3Z)-N-([1,1-biphenyl]-4-yl)-3-imino-N-[(1R)-2-oxo-2-{[(1S)-1-phenylethyl]amino}-1-(pyridin-3-yl)ethyl]propanamide'>Y0I</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=8fiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fiv OCA], [https://pdbe.org/8fiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fiv RCSB], [https://www.ebi.ac.uk/pdbsum/8fiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fiv ProSAT]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

SARS-CoV-2 main protease (M(pro)) is a validated antiviral drug target of nirmatrelvir, the active ingredient in Pfizer's oral drug Paxlovid. Drug-drug interactions limit the use of Paxlovid. In addition, drug-resistant M(pro) mutants against nirmatrelvir have been identified from cell culture viral passage and naturally occurring variants. As such, there is a need for a second generation of M(pro) inhibitors. In this study, we explored several reactive warheads in the design of M(pro) inhibitors. We identified Jun11119R (vinyl sulfonamide warhead), Jun10221R (propiolamide warhead), Jun1112R (4-chlorobut-2-ynamide warhead), Jun10541R (nitrile warhead), and Jun10963R (dually activated nitrile warhead) as potent M(pro) inhibitors. Jun10541R and Jun10963R also had potent antiviral activity against SARS-CoV-2 in Calu-3 cells with EC(50) values of 2.92 and 6.47 muM, respectively. X-ray crystal structures of M(pro) with Jun10541R and Jun10221 revealed covalent modification of Cys145. These M(pro) inhibitors with diverse reactive warheads collectively represent promising candidates for further development.

~~Authors:~~ Sacco, M., Wang, J., ~~Chen, Y~~.

Exploring diverse reactive warheads for the design of SARS-CoV-2 main protease inhibitors.,Tan B, Sacco M, Tan H, Li K, Joyce R, Zhang X, Chen Y, Wang J Eur J Med Chem. 2023 Nov 5;259:115667. doi: 10.1016/j.ejmech.2023.115667. Epub , 2023 Jul 19. PMID:37482021<ref>PMID:37482021</ref>

~~Description: Crystal structure~~ of the ~~SARS~~-~~CoV~~-~~2 (COVID-19) main protease in complex with inhibitor Jun10-54-1~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: Chen, Y]]

[[Category: ~~Wang, J~~]]

== References ==

[[Category: ~~Sacco, M~~]]

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Severe acute respiratory syndrome coronavirus 2]]

[[Category: Chen Y]]

[[Category: Sacco M]]

[[Category: Wang J]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8fiv is ON HOLD  until Paper Publication
+==Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor Jun10541R==
+<StructureSection load='8fiv' size='340' side='right'caption='[[8fiv]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8fiv]] is a 1 chain structure with sequence from [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=8FIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FIV 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]] 2.51&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y0I:(3Z)-N-([1,1-biphenyl]-4-yl)-3-imino-N-[(1R)-2-oxo-2-{[(1S)-1-phenylethyl]amino}-1-(pyridin-3-yl)ethyl]propanamide'>Y0I</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=8fiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fiv OCA], [https://pdbe.org/8fiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fiv RCSB], [https://www.ebi.ac.uk/pdbsum/8fiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fiv ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+SARS-CoV-2 main protease (M(pro)) is a validated antiviral drug target of nirmatrelvir, the active ingredient in Pfizer's oral drug Paxlovid. Drug-drug interactions limit the use of Paxlovid. In addition, drug-resistant M(pro) mutants against nirmatrelvir have been identified from cell culture viral passage and naturally occurring variants. As such, there is a need for a second generation of M(pro) inhibitors. In this study, we explored several reactive warheads in the design of M(pro) inhibitors. We identified Jun11119R (vinyl sulfonamide warhead), Jun10221R (propiolamide warhead), Jun1112R (4-chlorobut-2-ynamide warhead), Jun10541R (nitrile warhead), and Jun10963R (dually activated nitrile warhead) as potent M(pro) inhibitors. Jun10541R and Jun10963R also had potent antiviral activity against SARS-CoV-2 in Calu-3 cells with EC(50) values of 2.92 and 6.47 muM, respectively. X-ray crystal structures of M(pro) with Jun10541R and Jun10221 revealed covalent modification of Cys145. These M(pro) inhibitors with diverse reactive warheads collectively represent promising candidates for further development.
-Authors: Sacco, M., Wang, J., Chen, Y.
+Exploring diverse reactive warheads for the design of SARS-CoV-2 main protease inhibitors.,Tan B, Sacco M, Tan H, Li K, Joyce R, Zhang X, Chen Y, Wang J Eur J Med Chem. 2023 Nov 5;259:115667. doi: 10.1016/j.ejmech.2023.115667. Epub , 2023 Jul 19. PMID:37482021<ref>PMID:37482021</ref>
-Description: Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor Jun10-54-1
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chen, Y]]
+<div class="pdbe-citations 8fiv" style="background-color:#fffaf0;"></div>
-[[Category: Wang, J]]
+== References ==
-[[Category: Sacco, M]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Severe acute respiratory syndrome coronavirus 2]]
+[[Category: Chen Y]]
+[[Category: Sacco M]]
+[[Category: Wang J]]