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  4. A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron

A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron

Journal Commun. Biol. 5(1):669
Title A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron
Laboratory JEOL YOKOGUSHI Research Alliance Laboratories〈SA Prof. NAMBA Keiichi〉
Abstract

We are amid the historic coronavirus infectious disease 2019 (COVID-19) pandemic. Imbalances in the accessibility of vaccines, medicines, and diagnostics among countries, regions, and populations, and those in war crises, have been problematic. Nanobodies are small, stable, customizable, and inexpensive to produce. Herein, we present a panel of nanobodies that can detect the spike proteins of five SARS-CoV-2 variants of concern (VOCs) including Omicron. Here we show via ELISA, lateral flow, kinetic, flow cytometric, microscopy, and Western blotting assays that our nanobodies can quantify the spike variants. This panel of nanobodies broadly neutralizes viral infection caused by pseudotyped and authentic SARS-CoV-2 VOCs. Structural analyses show that the P86 clone targets epitopes that are conserved yet unclassified on the receptor-binding domain (RBD) and contacts the N-terminal domain (NTD). Human antibodies rarely access both regions; consequently, the clone buries hidden crevasses of SARS-CoV-2 spike proteins that go undetected by conventional antibodies.

Authors Ryota Maeda (1, 2), Junso Fujita (3, 4), Yoshinobu Konishi (1), Yasuhiro Kazuma (1), Hiroyuki Yamazaki (2, 5), Itsuki Anzai (6), Tokiko Watanabe (6), Keishi Yamaguchi (4), Kazuki Kasai (2), Kayoko Nagata (1), Yutaro Yamaoka (7), Kei Miyakawa (7), Akihide Ryo (7), Kotaro Shirakawa (1), Kei Sato (8, 9, 10), Fumiaki Makino (3, 11), Yoshiharu Matsuura (12, 13), Tsuyoshi Inoue (4), Akihiro Imura (2), Keiichi Namba (3, 14, 15), Akifumi Takaori-Kondo (1)
  1. Department of Haematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507 Japan.
  2. COGNANO Inc., Kyoto, 601-1255 Japan.
  3. Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871 Japan.
  4. Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871 Japan.
  5. Shizuoka City Shizuoka Hospital, Shizuoka, 420-8630 Japan.
  6. Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871 Japan.
  7. Department of Microbiology and Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004 Japan.
  8. Division of System Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639 Japan.
  9. Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033 Japan.
  10. CREST, Japan Science and Technology Agency, Saitama, 332-0012 Japan.
  11. JEOL Ltd., Tokyo, 196-8558 Japan.
  12. Centre for Infectious Disease Education and Research, Osaka University, Osaka, 565-0871 Japan.
  13. Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871 Japan.
  14. JEOL YOKOGUSHI Research Alliance Laboratories, Osaka University, Osaka, 565-0871 Japan.
  15. RIKEN Centre for Biosystems Dynamics Research and SPring-8 Centre, Osaka, 565-0871 Japan.
PubMed 35794202

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