7Y72

SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment of anti-RBD antibody E7 (focused refinement on Fab-RBD interface)

Summary for 7Y72

• Entry DOI: 10.2210/pdb7y72/pdb
• EMDB information: 33651
• Descriptor: Spike glycoprotein, Fab E7 light chain, Fab E7 heavy chain (3 entities in total)
• Functional Keywords: viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 312980.14

Authors

Chia, W.N.,Tan, C.W.,Tan, A.W.K.,Young, B.,Starr, T.N.,Lopez, E.,Fibriansah, G.,Barr, J.,Cheng, S.,Yeoh, A.Y.Y.,Yap, W.C.,Lim, B.L.,Ng, T.S.,Sia, W.R.,Zhu, F.,Chen, S.,Zhang, J.,Greaney, A.J.,Chen, M.,Au, G.G.,Paradkar, P.,Peiris, M.,Chung, A.W.,Bloom, J.D.,Lye, D.,Lok, S.M.,Wang, L.F. (deposition date: 2022-06-21, release date: 2023-08-02, Last modification date: 2024-10-30)

Primary citation

Chia, W.N.,Tan, C.W.,Tan, A.W.K.,Young, B.,Starr, T.N.,Lopez, E.,Fibriansah, G.,Barr, J.,Cheng, S.,Yeoh, A.Y.,Yap, W.C.,Lim, B.L.,Ng, T.S.,Sia, W.R.,Zhu, F.,Chen, S.,Zhang, J.,Kwek, M.S.S.,Greaney, A.J.,Chen, M.,Au, G.G.,Paradkar, P.N.,Peiris, M.,Chung, A.W.,Bloom, J.D.,Lye, D.,Lok, S.,Wang, L.F.
Potent pan huACE2-dependent sarbecovirus neutralizing monoclonal antibodies isolated from a BNT162b2-vaccinated SARS survivor.
Sci Adv, 9:eade3470-eade3470, 2023

PubMed Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo-electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure-dependent epitope.

PubMed: 37494438
DOI: 10.1126/sciadv.ade3470

Experimental method

ELECTRON MICROSCOPY (4.03 Å)