EMD-33824
SARS-CoV-2 spike in complex with neutralizing antibody NIV-10 (state 1)
EMD-33824
Single-particle3.0 Å
Deposition: 13/07/2022Map released: 19/07/2023
Last modified: 25/10/2023
Sample Organism:
Homo sapiens,
Severe acute respiratory syndrome coronavirus 2
Sample: SARS-COV-2 spike glycoprotein in complex with NIV-10
Deposition Authors: Moriyama S
,
Anraku Y ,
Muranishi S,
Adachi Y,
Kuroda D ,
Higuchi Y,
Kotaki R ,
Tonouchi K,
Yumoto K ,
Suzuki T,
Kita S ,
Fukuhara H ,
Kuroda Y,
Yamamoto T,
Onodera T,
Fukushi S,
Maeda K ,
Nakamura-Uchiyama F,
Hashiguchi T ,
Hoshino A ,
Maenaka K ,
Takahashi Y
Sample: SARS-COV-2 spike glycoprotein in complex with NIV-10
Deposition Authors: Moriyama S
,
Anraku Y ,
Muranishi S,
Adachi Y,
Kuroda D ,
Higuchi Y,
Kotaki R ,
Tonouchi K,
Yumoto K ,
Suzuki T,
Kita S ,
Fukuhara H ,
Kuroda Y,
Yamamoto T,
Onodera T,
Fukushi S,
Maeda K ,
Nakamura-Uchiyama F,
Hashiguchi T ,
Hoshino A ,
Maenaka K ,
Takahashi Y
Structural delineation and computational design of SARS-CoV-2-neutralizing antibodies against Omicron subvariants.
Moriyama S ,
Anraku Y ,
Taminishi S,
Adachi Y,
Kuroda D ,
Kita S ,
Higuchi Y,
Kirita Y ,
Kotaki R ,
Tonouchi K,
Yumoto K ,
Suzuki T,
Someya T,
Fukuhara H ,
Kuroda Y,
Yamamoto T,
Onodera T,
Fukushi S,
Maeda K ,
Nakamura-Uchiyama F,
Hashiguchi T ,
Hoshino A ,
Maenaka K ,
Takahashi Y
(2023) Nat Commun , 14 , 4198 - 4198
,
Anraku Y ,
Taminishi S,
Adachi Y,
Kuroda D ,
Kita S ,
Higuchi Y,
Kirita Y ,
Kotaki R ,
Tonouchi K,
Yumoto K ,
Suzuki T,
Someya T,
Fukuhara H ,
Kuroda Y,
Yamamoto T,
Onodera T,
Fukushi S,
Maeda K ,
Nakamura-Uchiyama F,
Hashiguchi T ,
Hoshino A ,
Maenaka K ,
Takahashi Y
(2023) Nat Commun , 14 , 4198 - 4198
Abstract:
SARS-CoV-2 Omicron subvariants have evolved to evade receptor-binding site (RBS) antibodies that exist in diverse individuals as public antibody clones. We rationally selected RBS antibodies resilient to mutations in emerging Omicron subvariants. Y489 was identified as a site of virus vulnerability and a common footprint of broadly neutralizing antibodies against the subvariants. Multiple Y489-binding antibodies were encoded by public clonotypes and additionally recognized F486, potentially accounting for the emergence of Omicron subvariants harboring the F486V mutation. However, a subclass of antibodies broadly neutralized BA.4/BA.5 variants via hydrophobic binding sites of rare clonotypes along with high mutation-resilience under escape mutation screening. A computationally designed antibody based on one of the Y489-binding antibodies, NIV-10/FD03, was able to bind XBB with any 486 mutation and neutralized XBB.1.5. The structural basis for the mutation-resilience of this Y489-binding antibody group may provide important insights into the design of therapeutics resistant to viral escape.
SARS-CoV-2 Omicron subvariants have evolved to evade receptor-binding site (RBS) antibodies that exist in diverse individuals as public antibody clones. We rationally selected RBS antibodies resilient to mutations in emerging Omicron subvariants. Y489 was identified as a site of virus vulnerability and a common footprint of broadly neutralizing antibodies against the subvariants. Multiple Y489-binding antibodies were encoded by public clonotypes and additionally recognized F486, potentially accounting for the emergence of Omicron subvariants harboring the F486V mutation. However, a subclass of antibodies broadly neutralized BA.4/BA.5 variants via hydrophobic binding sites of rare clonotypes along with high mutation-resilience under escape mutation screening. A computationally designed antibody based on one of the Y489-binding antibodies, NIV-10/FD03, was able to bind XBB with any 486 mutation and neutralized XBB.1.5. The structural basis for the mutation-resilience of this Y489-binding antibody group may provide important insights into the design of therapeutics resistant to viral escape.