1. Monobodies with potent neutralizing activity against SARS-CoV-2 Delta and other variants of concern.
- Author
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Kondo T, Matsuoka K, Umemoto S, Fujino T, Hayashi G, Iwatani Y, and Murakami H
- Subjects
- Antibody Affinity immunology, COVID-19 immunology, COVID-19 virology, Humans, Receptors, Coronavirus immunology, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, SARS-CoV-2 immunology
- Abstract
Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are useful for patients' treatment of the coronavirus disease 2019 (COVID-19). We report here affinity maturation of monobodies against the SARS-CoV-2 spike protein and their neutralizing activity against SARS-CoV-2 B.1.1 (Pango v.3.1.14) as well as four variants of concern. We selected matured monobodies from libraries with multi-site saturation mutagenesis on the recognition loops through in vitro selection. One clone, the C4-AM2 monobody, showed extremely high affinity ( K
D < 0.01 nM) against the receptor-binding domain of the SARS-CoV-2 B.1.1, even in monomer form. Furthermore, the C4-AM2 monobody efficiently neutralized the SARS-CoV-2 B.1.1 ( IC50 = 46 pM, 0.62 ng/ml), and the Alpha ( IC50 = 77 pM, 1.0 ng/ml), Beta ( IC50 = 0.54 nM, 7.2 ng/ml), Gamma ( IC50 = 0.55 nM, 7.4 ng/ml), and Delta ( IC50 = 0.59 nM, 8.0 ng/ml) variants. The obtained monobodies would be useful as neutralizing proteins against current and potentially hazardous future SARS-CoV-2 variants., (© 2022 Kondo et al.)- Published
- 2022
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