EMD-33650
SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment of anti-RBD antibody E7
EMD-33650
Single-particle3.12 Å
Deposition: 21/06/2022Map released: 02/08/2023
Last modified: 23/10/2024
Sample Organism:
Homo sapiens
Sample: SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment of anti-RBD antibody E7
Fitted models: 7y71 (Avg. Q-score: 0.415)
Deposition Authors: Chia WN
,
Tan CW ,
Tan AWK ,
Young B ,
Starr TN ,
Lopez E ,
Fibriansah G ,
Barr J ,
Cheng S ,
Yeoh AYY,
Yap WC ,
Lim BL,
Ng TS ,
Sia WR ,
Zhu F ,
Chen S ,
Zhang J ,
Greaney AJ ,
Chen M ,
Au GG ,
Paradkar P,
Peiris M ,
Chung AW ,
Bloom JD ,
Lye D ,
Lok SM,
Wang LF
Sample: SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment of anti-RBD antibody E7
Fitted models: 7y71 (Avg. Q-score: 0.415)
Deposition Authors: Chia WN
,
Tan CW ,
Tan AWK ,
Young B ,
Starr TN ,
Lopez E ,
Fibriansah G ,
Barr J ,
Cheng S ,
Yeoh AYY,
Yap WC ,
Lim BL,
Ng TS ,
Sia WR ,
Zhu F ,
Chen S ,
Zhang J ,
Greaney AJ ,
Chen M ,
Au GG ,
Paradkar P,
Peiris M ,
Chung AW ,
Bloom JD ,
Lye D ,
Lok SM,
Wang LF
Potent pan huACE2-dependent sarbecovirus neutralizing monoclonal antibodies isolated from a BNT162b2-vaccinated SARS survivor.
Chia WN ,
Tan CW ,
Tan AWK ,
Young B ,
Starr TN ,
Lopez E ,
Fibriansah G ,
Barr J ,
Cheng S ,
Yeoh AY,
Yap WC ,
Lim BL,
Ng TS ,
Sia WR ,
Zhu F ,
Chen S ,
Zhang J ,
Kwek MSS ,
Greaney AJ ,
Chen M ,
Au GG ,
Paradkar PN ,
Peiris M ,
Chung AW ,
Bloom JD ,
Lye D ,
Lok S ,
Wang LF
(2023) Sci Adv , 9 , eade3470 - eade3470
,
Tan CW ,
Tan AWK ,
Young B ,
Starr TN ,
Lopez E ,
Fibriansah G ,
Barr J ,
Cheng S ,
Yeoh AY,
Yap WC ,
Lim BL,
Ng TS ,
Sia WR ,
Zhu F ,
Chen S ,
Zhang J ,
Kwek MSS ,
Greaney AJ ,
Chen M ,
Au GG ,
Paradkar PN ,
Peiris M ,
Chung AW ,
Bloom JD ,
Lye D ,
Lok S ,
Wang LF
(2023) Sci Adv , 9 , eade3470 - eade3470
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.
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.