9pjf: Difference between revisions

Latest revision as of 14:03, 10 February 2026

GII.4 Human Norovirus 3CL protease bound to compound 27

Structural highlights

9pjf is a 4 chain structure with sequence from Norovirus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.47Å
Ligands:	A1C3V, ALC, ELL
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

K4L8Z7_9CALI 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave polyadenylate-binding protein thereby inhibiting cellular translation.[PROSITE-ProRule:PRU00870]

Publication Abstract from PubMed

The cysteine 3C-like proteases (3CL(pro)) of caliciviruses, coronaviruses, and picornaviruses are essential for viral replication. In this study, we report the development of potent broad-spectrum peptidomimetic antiviral agents that target the 3CL(pro) of caliciviruses (NS6), coronaviruses (M(pro)), and a picornavirus (3C). Based upon previously reported inhibitors, a small library of compounds was designed, synthesized and tested to identify a core structure, which was then derivatized with a focus upon P3 and P4 positions to afford new inhibitors with improved potency against the respective viral enzymes and enhanced binding as determined by X-ray crystallography. These compounds were tested against a range of viruses in culture, revealing minimal toxicity while exhibiting broad-spectrum potent nanomolar activities against noroviruses and several coronavirus species, including alpha and omicron variants of SARS-CoV-2 and Middle East Respiratory Syndrome virus (MERS).

Broad-Spectrum Peptidomimetic Inhibitors of Norovirus and Coronavirus 3C-like Proteases.,Brimble MA, Stubbing LA, Hermant YO, Yang SH, Hubert JG, Pearl ES, McSweeney AM, Young VL, Campbell AC, Opel-Reading HK, McKenzie-Goldsmith GM, Putha L, Mortuza R, Wang H, Hurst BL, Julander J, Harris LD, Krause KL, Ward VK ACS Infect Dis. 2025 Dec 18. doi: 10.1021/acsinfecdis.5c00680. PMID:41412823^[1]

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

References

↑ Brimble MA, Stubbing LA, Hermant YO, Yang SH, Hubert JG, Pearl ES, McSweeney AM, Young VL, Campbell AC, Opel-Reading HK, McKenzie-Goldsmith GM, Putha L, Mortuza R, Wang H, Hurst BL, Julander J, Harris LD, Krause KL, Ward VK. Broad-Spectrum Peptidomimetic Inhibitors of Norovirus and Coronavirus 3C-like Proteases. ACS Infect Dis. 2025 Dec 18. PMID:41412823 doi:10.1021/acsinfecdis.5c00680

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Brimble MA, Stubbing LA, Hermant YO, Yang SH, Hubert JG, Pearl ES, McSweeney AM, Young VL, Campbell AC, Opel-Reading HK, McKenzie-Goldsmith GM, Putha L, Mortuza R, Wang H, Hurst BL, Julander J, Harris LD, Krause KL, Ward VK. Broad-Spectrum Peptidomimetic Inhibitors of Norovirus and Coronavirus 3C-like Proteases. ACS Infect Dis. 2025 Dec 18. PMID:41412823 doi:10.1021/acsinfecdis.5c00680

[1]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9pjf is ON HOLD
+==GII.4 Human Norovirus 3CL protease bound to compound 27==
+<StructureSection load='9pjf' size='340' side='right'caption='[[9pjf]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9pjf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Norovirus Norovirus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PJF 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]] 1.47&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1C3V:N-(tert-butoxycarbonyl)-L-phenylalanine'>A1C3V</scene>, <scene name='pdbligand=ALC:2-AMINO-3-CYCLOHEXYL-PROPIONIC+ACID'>ALC</scene>, <scene name='pdbligand=ELL:(2~{S})-2-azanyl-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propanal'>ELL</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=9pjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pjf OCA], [https://pdbe.org/9pjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pjf RCSB], [https://www.ebi.ac.uk/pdbsum/9pjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pjf ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/K4L8Z7_9CALI K4L8Z7_9CALI] 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave polyadenylate-binding protein thereby inhibiting cellular translation.[PROSITE-ProRule:PRU00870]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The cysteine 3C-like proteases (3CL(pro)) of caliciviruses, coronaviruses, and picornaviruses are essential for viral replication. In this study, we report the development of potent broad-spectrum peptidomimetic antiviral agents that target the 3CL(pro) of caliciviruses (NS6), coronaviruses (M(pro)), and a picornavirus (3C). Based upon previously reported inhibitors, a small library of compounds was designed, synthesized and tested to identify a core structure, which was then derivatized with a focus upon P3 and P4 positions to afford new inhibitors with improved potency against the respective viral enzymes and enhanced binding as determined by X-ray crystallography. These compounds were tested against a range of viruses in culture, revealing minimal toxicity while exhibiting broad-spectrum potent nanomolar activities against noroviruses and several coronavirus species, including alpha and omicron variants of SARS-CoV-2 and Middle East Respiratory Syndrome virus (MERS).
-Authors: Campbell, A.C., Opel-Reading, H.K., Krause, K.L.
+Broad-Spectrum Peptidomimetic Inhibitors of Norovirus and Coronavirus 3C-like Proteases.,Brimble MA, Stubbing LA, Hermant YO, Yang SH, Hubert JG, Pearl ES, McSweeney AM, Young VL, Campbell AC, Opel-Reading HK, McKenzie-Goldsmith GM, Putha L, Mortuza R, Wang H, Hurst BL, Julander J, Harris LD, Krause KL, Ward VK ACS Infect Dis. 2025 Dec 18. doi: 10.1021/acsinfecdis.5c00680. PMID:41412823<ref>PMID:41412823</ref>
-Description: GII.4 Human Norovirus 3CL protease bound to compound 27
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Krause, K.L]]
+<div class="pdbe-citations 9pjf" style="background-color:#fffaf0;"></div>
-[[Category: Campbell, A.C]]
+== References ==
-[[Category: Opel-Reading, H.K]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Norovirus]]
+[[Category: Synthetic construct]]
+[[Category: Campbell AC]]
+[[Category: Krause KL]]
+[[Category: Opel-Reading HK]]

9pjf: Difference between revisions

Latest revision as of 14:03, 10 February 2026

GII.4 Human Norovirus 3CL protease bound to compound 27

Structural highlights

Function

Publication Abstract from PubMed

References

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