Life Sci Alliance . Monobodies with potent neutralizing activity against SARS-CoV-2 Delta and other variants of concern

[tetano]

Life Sci Alliance


. 2022 Mar 7;5(6):e202101322.
doi: 10.26508/lsa.202101322. Print 2022 Jun.
Monobodies with potent neutralizing activity against SARS-CoV-2 Delta and other variants of concern


Taishi Kondo ¹ , Kazuhiro Matsuoka ² , Shun Umemoto ¹ , Tomoshige Fujino ¹ , Gosuke Hayashi ^{1 3} , Yasumasa Iwatani ^{4 5} , Hiroshi Murakami ^{1 6}



Affiliations

• PMID: 35256514
• DOI: 10.26508/lsa.202101322

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 (IC ₅₀ = 46 pM, 0.62 ng/ml), and the Alpha (IC ₅₀ = 77 pM, 1.0 ng/ml), Beta (IC ₅₀ = 0.54 nM, 7.2 ng/ml), Gamma (IC ₅₀ = 0.55 nM, 7.4 ng/ml), and Delta (IC ₅₀ = 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.