Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate.
Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, wh...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-11-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012726 |
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| _version_ | 1846123587880091648 |
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| author | Gang Ye Fan Bu Divyasha Saxena Hailey Turner-Hubbard Morgan Herbst Benjamin Spiller Brian E Wadzinski Lanying Du Bin Liu Jian Zheng Fang Li |
| author_facet | Gang Ye Fan Bu Divyasha Saxena Hailey Turner-Hubbard Morgan Herbst Benjamin Spiller Brian E Wadzinski Lanying Du Bin Liu Jian Zheng Fang Li |
| author_sort | Gang Ye |
| collection | DOAJ |
| description | Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, which demonstrates high potency against a wide range of Omicron subvariants both in vitro and in a mouse model. Cryo-EM data revealed that Nanosota-9 neutralizes Omicron through a unique mechanism: two Nanosota-9 molecules crosslink two receptor-binding domains (RBDs) of the trimeric Omicron spike protein, preventing the RBDs from binding to the ACE2 receptor. This mechanism explains its strong anti-Omicron potency. Additionally, the Nanosota-9 binding epitopes on the spike protein are relatively conserved among Omicron subvariants, contributing to its broad anti-Omicron spectrum. Combined with our recently developed structure-guided in vitro evolution approach for nanobodies, Nanosota-9 has the potential to serve as the foundation for a superior anti-Omicron therapeutic. |
| format | Article |
| id | doaj-art-c3d479be8c6c44a78b1acb41494a350d |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-c3d479be8c6c44a78b1acb41494a350d2024-12-14T05:31:20ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-11-012011e101272610.1371/journal.ppat.1012726Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate.Gang YeFan BuDivyasha SaxenaHailey Turner-HubbardMorgan HerbstBenjamin SpillerBrian E WadzinskiLanying DuBin LiuJian ZhengFang LiOmicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, which demonstrates high potency against a wide range of Omicron subvariants both in vitro and in a mouse model. Cryo-EM data revealed that Nanosota-9 neutralizes Omicron through a unique mechanism: two Nanosota-9 molecules crosslink two receptor-binding domains (RBDs) of the trimeric Omicron spike protein, preventing the RBDs from binding to the ACE2 receptor. This mechanism explains its strong anti-Omicron potency. Additionally, the Nanosota-9 binding epitopes on the spike protein are relatively conserved among Omicron subvariants, contributing to its broad anti-Omicron spectrum. Combined with our recently developed structure-guided in vitro evolution approach for nanobodies, Nanosota-9 has the potential to serve as the foundation for a superior anti-Omicron therapeutic.https://doi.org/10.1371/journal.ppat.1012726 |
| spellingShingle | Gang Ye Fan Bu Divyasha Saxena Hailey Turner-Hubbard Morgan Herbst Benjamin Spiller Brian E Wadzinski Lanying Du Bin Liu Jian Zheng Fang Li Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate. PLoS Pathogens |
| title | Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate. |
| title_full | Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate. |
| title_fullStr | Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate. |
| title_full_unstemmed | Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate. |
| title_short | Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate. |
| title_sort | discovery of nanosota 9 as anti omicron nanobody therapeutic candidate |
| url | https://doi.org/10.1371/journal.ppat.1012726 |
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