EMD-30982
Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants
EMD-30982
Single-particle3.9 Å
Deposition: 09/02/2021Map released: 15/09/2021
Last modified: 06/11/2024
Sample Organism:
Homo sapiens,
Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 Spike glycoprotein complex with 13G9 Fab
Fitted models: 7e3k (Avg. Q-score: 0.298)
Deposition Authors: Guo H
,
Li T
Sample: SARS-CoV-2 Spike glycoprotein complex with 13G9 Fab
Fitted models: 7e3k (Avg. Q-score: 0.298)
Deposition Authors: Guo H
,
Li T
Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants.
Li T ,
Han X ,
Gu C,
Guo H ,
Zhang H ,
Wang Y ,
Hu C,
Wang K ,
Liu F ,
Luo F,
Zhang Y,
Hu J,
Wang W ,
Li S,
Hao Y,
Shen M,
Huang J,
Long Y,
Song S,
Wu R,
Mu S,
Chen Q,
Gao F,
Wang J,
Long S,
Li L,
Wu Y,
Gao Y ,
Xu W,
Cai X,
Qu D,
Zhang Z,
Zhang H ,
Li N,
Gao Q,
Zhang G,
He C,
Wang W ,
Ji X,
Tang N ,
Yuan Z ,
Xie Y ,
Yang H ,
Zhang B ,
Huang A ,
Jin A
(2021) Nat Commun , 12 , 6304 - 6304
,
Han X ,
Gu C,
Guo H ,
Zhang H ,
Wang Y ,
Hu C,
Wang K ,
Liu F ,
Luo F,
Zhang Y,
Hu J,
Wang W ,
Li S,
Hao Y,
Shen M,
Huang J,
Long Y,
Song S,
Wu R,
Mu S,
Chen Q,
Gao F,
Wang J,
Long S,
Li L,
Wu Y,
Gao Y ,
Xu W,
Cai X,
Qu D,
Zhang Z,
Zhang H ,
Li N,
Gao Q,
Zhang G,
He C,
Wang W ,
Ji X,
Tang N ,
Yuan Z ,
Xie Y ,
Yang H ,
Zhang B ,
Huang A ,
Jin A
(2021) Nat Commun , 12 , 6304 - 6304
Abstract:
Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 13G9 both recognize the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.
Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 13G9 both recognize the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.