7cac

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SARS-CoV-2 S trimer with one RBD in the open state and complexed with one H014 Fab.

Structural highlights

7cac is a 5 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.55Å
Ligands:NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody.,Lv Z, Deng YQ, Ye Q, Cao L, Sun CY, Fan C, Huang W, Sun S, Sun Y, Zhu L, Chen Q, Wang N, Nie J, Cui Z, Zhu D, Shaw N, Li XF, Li Q, Xie L, Wang Y, Rao Z, Qin CF, Wang X Science. 2020 Sep 18;369(6510):1505-1509. doi: 10.1126/science.abc5881. Epub 2020, Jul 23. PMID:32703908[1]

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

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Citations
86 reviews cite this structure
Jackson et al. (2022)
No citations found

See Also

References

  1. Lv Z, Deng YQ, Ye Q, Cao L, Sun CY, Fan C, Huang W, Sun S, Sun Y, Zhu L, Chen Q, Wang N, Nie J, Cui Z, Zhu D, Shaw N, Li XF, Li Q, Xie L, Wang Y, Rao Z, Qin CF, Wang X. Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. Science. 2020 Sep 18;369(6510):1505-1509. doi: 10.1126/science.abc5881. Epub 2020, Jul 23. PMID:32703908 doi:http://dx.doi.org/10.1126/science.abc5881

Contents


PDB ID 7cac

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