Structural delineation and computational design of SARS-CoV-2-neutralizing antibodies against Omicron subvariants
© 2023. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 14. Juli, Seite 4198 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moriyama, Saya [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Neutralizing |
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| Anmerkungen: |
Date Completed 17.07.2023 Date Revised 18.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-39890-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359527582 |
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| 245 | 1 | 0 | |a Structural delineation and computational design of SARS-CoV-2-neutralizing antibodies against Omicron subvariants |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Anraku, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Taminishi, Shunta |e verfasserin |4 aut | |
| 700 | 1 | |a Adachi, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Kuroda, Daisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Kita, Shunsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Higuchi, Yusuke |e verfasserin |4 aut | |
| 700 | 1 | |a Kirita, Yuhei |e verfasserin |4 aut | |
| 700 | 1 | |a Kotaki, Ryutaro |e verfasserin |4 aut | |
| 700 | 1 | |a Tonouchi, Keisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Yumoto, Kohei |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Tateki |e verfasserin |4 aut | |
| 700 | 1 | |a Someya, Taiyou |e verfasserin |4 aut | |
| 700 | 1 | |a Fukuhara, Hideo |e verfasserin |4 aut | |
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| 700 | 1 | |a Onodera, Taishi |e verfasserin |4 aut | |
| 700 | 1 | |a Fukushi, Shuetsu |e verfasserin |4 aut | |
| 700 | 1 | |a Maeda, Ken |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura-Uchiyama, Fukumi |e verfasserin |4 aut | |
| 700 | 1 | |a Hashiguchi, Takao |e verfasserin |4 aut | |
| 700 | 1 | |a Hoshino, Atsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Maenaka, Katsumi |e verfasserin |4 aut | |
| 700 | 1 | |a Takahashi, Yoshimasa |e verfasserin |4 aut | |
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