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Commun Biol
. 2022 Jul 6;5(1):669.
doi: 10.1038/s42003-022-03630-3.
A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron
Ryota Maeda # 1 2 , Junso Fujita # 3 4 , Yoshinobu Konishi 5 , Yasuhiro Kazuma 5 , Hiroyuki Yamazaki 6 7 , Itsuki Anzai 8 , Tokiko Watanabe 8 , Keishi Yamaguchi 4 , Kazuki Kasai 6 , Kayoko Nagata 5 , Yutaro Yamaoka 9 , Kei Miyakawa 9 , Akihide Ryo 9 , Kotaro Shirakawa 5 , Kei Sato 10 11 12 , Fumiaki Makino 3 13 , Yoshiharu Matsuura 14 15 , Tsuyoshi Inoue 4 , Akihiro Imura 16 , Keiichi Namba 17 18 19 , Akifumi Takaori-Kondo 20
Affiliations
- PMID: 35794202
- DOI: 10.1038/s42003-022-03630-3
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.