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タイトル | Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1. |
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ジャーナル・号・ページ | Structure, Vol. 32, Issue 3, Page 263-272.e7, Year 2024 |
掲載日 | 2024年3月7日 |
著者 | Tatsuhiko Ozawa / Yoshiki Ikeda / Liuan Chen / Rigel Suzuki / Atsushi Hoshino / Akira Noguchi / Shunsuke Kita / Yuki Anraku / Emiko Igarashi / Yumiko Saga / Noriko Inasaki / Shunta Taminishi / Jiei Sasaki / Yuhei Kirita / Hideo Fukuhara / Katsumi Maenaka / Takao Hashiguchi / Takasuke Fukuhara / Kenichi Hirabayashi / Hideki Tani / Hiroyuki Kishi / Hideki Niimi / |
PubMed 要旨 | 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 ...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 (V 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. |
リンク | Structure / PubMed:38228146 |
手法 | EM (単粒子) |
解像度 | 3.22 - 3.41 Å |
構造データ | EMDB-36905: SARS-CoV-2 BA.1 RBD with UT28-RD EMDB-36906: SARS-CoV-2 BA.1 spike with UT28-RD |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Antibody / Spike protein / STRUCTURAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex |