View source for 5zvk


==Crystal Structure of the Human Coronavirus MERS HR1 motif in complex with pan-CoVs inhibitor EK1==
<StructureSection load='5zvk' size='340' side='right'caption='[[5zvk]], [[Resolution|resolution]] 3.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zvk]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus] 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=5ZVK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZVK 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]] 3.31&#8491;</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=5zvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zvk OCA], [https://pdbe.org/5zvk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zvk RCSB], [https://www.ebi.ac.uk/pdbsum/5zvk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zvk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPIKE_MERS1 SPIKE_MERS1] Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.[HAMAP-Rule:MF_04099]<ref>PMID:23486063</ref>   Mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099]  Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]
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== Publication Abstract from PubMed ==
Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short alpha-HCoV and long beta-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.

A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike.,Xia S, Yan L, Xu W, Agrawal AS, Algaissi A, Tseng CK, Wang Q, Du L, Tan W, Wilson IA, Jiang S, Yang B, Lu L Sci Adv. 2019 Apr 10;5(4):eaav4580. doi: 10.1126/sciadv.aav4580. eCollection 2019, Apr. PMID:30989115<ref>PMID:30989115</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5zvk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sandbox 3001|Sandbox 3001]]
*[[Spike protein|Spike protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Middle East respiratory syndrome-related coronavirus]]
[[Category: Synthetic construct]]
[[Category: Wilson IA]]
[[Category: Yan L]]
[[Category: Yang B]]