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-Structure paper
タイトル | A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2. |
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ジャーナル・号・ページ | Emerg Microbes Infect, Vol. 13, Issue 1, Page 2373307, Year 2024 |
掲載日 | 2024年7月12日 |
![]() | Hancong Sun / Lingyun Xia / Jianhua Li / Yuanyuan Zhang / Guanying Zhang / Ping Huang / Xingxing Wang / Yue Cui / Ting Fang / Pengfei Fan / Qiang Zhou / Xiangyang Chi / Changming Yu / ![]() |
PubMed 要旨 | SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which ...SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv) form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion. |
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手法 | EM (単粒子) |
解像度 | 2.7 - 3.4 Å |
構造データ | EMDB-39645, PDB-8yww: EMDB-39646, PDB-8ywx: |
由来 |
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex |