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Structure paper

TitleDiscovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate.
Journal, issue, pagesPLoS Pathog, Vol. 20, Issue 11, Page e1012726, Year 2024
Publish dateNov 26, 2024
AuthorsGang Ye / Fan Bu / Divyasha Saxena / Hailey Turner-Hubbard / Morgan Herbst / Benjamin Spiller / Brian E Wadzinski / Lanying Du / Bin Liu / Jian Zheng / Fang Li /
PubMed AbstractOmicron 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 ...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.
External linksPLoS Pathog / PubMed:39591462 / PubMed Central
MethodsEM (single particle)
Resolution2.99 - 3.44 Å
Structure data

45771

9co6

EMDB-45771, PDB-9co6:
BA.5 spike/Nanosota-9 complex
Method: EM (single particle) / Resolution: 3.01 Å

45772

9co7

EMDB-45772, PDB-9co7:
Local refinement of BA.5 spike/Nanosota-9 complex
Method: EM (single particle) / Resolution: 3.32 Å

45773

9co8

EMDB-45773, PDB-9co8:
JN.1 spike/Nanosota-9 complex
Method: EM (single particle) / Resolution: 2.99 Å

45774

9co9

EMDB-45774, PDB-9co9:
Local refinement of JN.1 spike/Nanosota-9 complex
Method: EM (single particle) / Resolution: 3.44 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • vicugna pacos (alpaca)
KeywordsVIRAL PROTEIN / spike / nanobody / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex / EBOV glycoprotein

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