View source for 7c01


==Molecular basis for a potent human neutralizing antibody targeting SARS-CoV-2 RBD==
<StructureSection load='7c01' size='340' side='right'caption='[[7c01]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7c01]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [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=7C01 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C01 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]] 2.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7c01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c01 OCA], [https://pdbe.org/7c01 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c01 RCSB], [https://www.ebi.ac.uk/pdbsum/7c01 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c01 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</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]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
An outbreak of the coronavirus disease 2019 (COVID-19)(1-3), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(4) spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. In this study, we report the isolation of 2 specific human monoclonal antibodies (MAbs) from a convalescent COVID-19 patient. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro against SARS-CoV-2. In addition, CB6 inhibited SARS-CoV-2 infection in rhesus monkeys at both prophylactic and treatment settings. Further structural studies revealed that CB6 recognizes an epitope that overlaps with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 receptor binding domain (RBD), thereby interfering with the virus/receptor interactions by both steric hindrance and direct interface-residue competition. Our results suggest CB6 deserves further clinical translation.

A human neutralizing antibody targets the receptor binding site of SARS-CoV-2.,Shi R, Shan C, Duan X, Chen Z, Liu P, Song J, Song T, Bi X, Han C, Wu L, Gao G, Hu X, Zhang Y, Tong Z, Huang W, Liu WJ, Wu G, Zhang B, Wang L, Qi J, Feng H, Wang FS, Wang Q, Gao GF, Yuan Z, Yan J Nature. 2020 May 26. pii: 10.1038/s41586-020-2381-y. doi:, 10.1038/s41586-020-2381-y. PMID:32454512<ref>PMID:32454512</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7c01" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Gao FG]]
[[Category: Qi J]]
[[Category: Shi R]]
[[Category: Wang Q]]
[[Category: Yan J]]