View source for 9vkk


==Crystal structure of EV71 3C protease in complex with bofutrelvir==
<StructureSection load='9vkk' size='340' side='right'caption='[[9vkk]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vkk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_enterovirus_71_(strain_BRCR) Human enterovirus 71 (strain BRCR)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VKK 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FHR:~{N}-[(2~{S})-3-cyclohexyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanylidene-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]propan-2-yl]-1~{H}-indole-2-carboxamide'>FHR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=9vkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vkk OCA], [https://pdbe.org/9vkk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vkk RCSB], [https://www.ebi.ac.uk/pdbsum/9vkk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vkk ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enteroviruses, which belong to the family Picornaviridae, cause hand, foot, and mouth disease (HFMD), respiratory symptoms, and severe neurological complications in children. Since vaccines cannot provide cross-protection against different serotypes of enteroviruses, the development of broad-spectrum anti-enteroviral drugs is imperative. The viral 3C protease (3Cpro), which is essential for polyprotein processing represents a validated target for therapeutic intervention. Importantly, enterovirus 3Cpro shares conserved structural and catalytic features with coronavirus main protease (Mpro, also known as 3C-like protease, 3CLpro), providing a rationale for cross-target inhibitor repurposing. Through targeted screening of peptidomimetic protease inhibitors, a clinical-stage SARS-CoV-2 Mpro inhibitor was identified as a potent inhibitor of enterovirus A71 (EV71) 3Cpro. Bofutrelvir displayed nanomolar antiviral activity in multiple cell lines and demonstrated broad-spectrum efficacy against several enteroviruses including coxsackievirus B5, coxsackievirus A16 (CA16) and echovirus 11. In EV71 infected neonatal mice, intraperitoneal administration of bofutrelvir markedly reduced viral loads in brain, spinal cord, and muscle, alleviated clinical symptoms, and suppressed tissue inflammation. Oral administration of bofutrelvir also provided therapeutic benefits in neonatal mice models of both EV71 and CA16. Crystallographic analysis revealed that bofutrelvir binds in the conserved substrate-binding cleft of EV71 3Cpro, elucidating its molecular mechanism of inhibition. These findings identify bofutrelvir as a broad-spectrum peptidomimetic 3Cpro inhibitor with strong antiviral efficacy against enteroviruses and highlight its potential for repurposing as a promising antiviral candidate for the treatment of enteroviral infections.

A clinical SARS-CoV-2 Mpro inhibitor blocks replication of multiple enteroviruses and confers oral in vivo protection in animal models.,Ye Z, Dai W, Zhang S, Xiang Y, Wang J, Zhang Y, Cao W, Neyts J, Li Z, Feng F, Xiao G, Liu H, Cao J, Zhang LK PLoS Pathog. 2026 Mar 11;22(3):e1014051. doi: 10.1371/journal.ppat.1014051. , eCollection 2026 Mar. PMID:41811867<ref>PMID:41811867</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9vkk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Ye Z]]
[[Category: Zhang L]]