7L4Z

Structure of SARS-CoV-2 spike RBD in complex with cyclic peptide

Summary for 7L4Z

• Entry DOI: 10.2210/pdb7l4z/pdb
• Descriptor: Spike protein S1, ACE-DTY-LYS-ALA-GLY-VAL-VAL-TYR-GLY-TYR-ASN-ALA-TRP-ILE-ARG-CYS-NH2, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: covid-19, spike, rbd, cyclic peptide, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 10
• Total formula weight: 140250.00

Authors

Christie, M.,Mackay, J.P.,Passioura, T.,Payne, R.J. (deposition date: 2020-12-21, release date: 2021-06-30, Last modification date: 2024-10-23)

Primary citation

Norman, A.,Franck, C.,Christie, M.,Hawkins, P.M.E.,Patel, K.,Ashhurst, A.S.,Aggarwal, A.,Low, J.K.K.,Siddiquee, R.,Ashley, C.L.,Steain, M.,Triccas, J.A.,Turville, S.,Mackay, J.P.,Passioura, T.,Payne, R.J.
Discovery of Cyclic Peptide Ligands to the SARS-CoV-2 Spike Protein Using mRNA Display.
Acs Cent.Sci., 7:1001-1008, 2021

PubMed Abstract: The COVID-19 pandemic, caused by SARS-CoV-2, has led to substantial morbidity, mortality, and disruption globally. Cellular entry of SARS-CoV-2 is mediated by the viral spike protein, and affinity ligands to this surface protein have the potential for applications as antivirals and diagnostic reagents. Here, we describe the affinity selection of cyclic peptide ligands to the SARS-CoV-2 spike protein receptor binding domain (RBD) from three distinct libraries (in excess of a trillion molecules each) by mRNA display. We identified six high affinity molecules with dissociation constants ( ) in the nanomolar range (15-550 nM) to the RBD. The highest affinity ligand could be used as an affinity reagent to detect the spike protein in solution by ELISA, and the cocrystal structure of this molecule bound to the RBD demonstrated that it binds to a cryptic binding site, displacing a β-strand near the C-terminus. Our findings provide key mechanistic insight into the binding of peptide ligands to the SARS-CoV-2 spike RBD, and the ligands discovered in this work may find future use as reagents for diagnostic applications.

PubMed: 34230894
DOI: 10.1021/acscentsci.0c01708

Experimental method

X-RAY DIFFRACTION (3.96 Å)