Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1
Copyright © 2024 Elsevier Ltd. All rights reserved..
SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (VH T28R/N57D), UT28K-RD targeting the mutation site. In vitro and in vivo experiments demonstrated the efficacy of UT28K-RD in neutralizing Omicron BA.1. Although the experimentally determined structure partially differed from the predicted model, our study serves as a successful case of antibody design, wherein the predicted amino acid substitution enhanced the recognition of the previously elusive Omicron BA.1. We anticipate that numerous similar cases will be reported, showcasing the potential of this approach for improving protein-protein interactions. Our findings will contribute to the development of novel therapeutic strategies for highly mutable viruses, such as SARS-CoV-2.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
Structure (London, England : 1993) - 32(2024), 3 vom: 07. März, Seite 263-272.e7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ozawa, Tatsuhiko [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 11.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.str.2023.12.013 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367186977 |
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| 100 | 1 | |a Ozawa, Tatsuhiko |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1 |
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| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (VH T28R/N57D), UT28K-RD targeting the mutation site. In vitro and in vivo experiments demonstrated the efficacy of UT28K-RD in neutralizing Omicron BA.1. Although the experimentally determined structure partially differed from the predicted model, our study serves as a successful case of antibody design, wherein the predicted amino acid substitution enhanced the recognition of the previously elusive Omicron BA.1. We anticipate that numerous similar cases will be reported, showcasing the potential of this approach for improving protein-protein interactions. Our findings will contribute to the development of novel therapeutic strategies for highly mutable viruses, such as SARS-CoV-2 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a in silico designed | |
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| 700 | 1 | |a Ikeda, Yoshiki |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Liuan |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Rigel |e verfasserin |4 aut | |
| 700 | 1 | |a Hoshino, Atsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Noguchi, Akira |e verfasserin |4 aut | |
| 700 | 1 | |a Kita, Shunsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Anraku, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Igarashi, Emiko |e verfasserin |4 aut | |
| 700 | 1 | |a Saga, Yumiko |e verfasserin |4 aut | |
| 700 | 1 | |a Inasaki, Noriko |e verfasserin |4 aut | |
| 700 | 1 | |a Taminishi, Shunta |e verfasserin |4 aut | |
| 700 | 1 | |a Sasaki, Jiei |e verfasserin |4 aut | |
| 700 | 1 | |a Kirita, Yuhei |e verfasserin |4 aut | |
| 700 | 1 | |a Fukuhara, Hideo |e verfasserin |4 aut | |
| 700 | 1 | |a Maenaka, Katsumi |e verfasserin |4 aut | |
| 700 | 1 | |a Hashiguchi, Takao |e verfasserin |4 aut | |
| 700 | 1 | |a Fukuhara, Takasuke |e verfasserin |4 aut | |
| 700 | 1 | |a Hirabayashi, Kenichi |e verfasserin |4 aut | |
| 700 | 1 | |a Tani, Hideki |e verfasserin |4 aut | |
| 700 | 1 | |a Kishi, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Niimi, Hideki |e verfasserin |4 aut | |
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