@article {Kondoe202101322, author = {Taishi Kondo and Kazuhiro Matsuoka and Shun Umemoto and Tomoshige Fujino and Gosuke Hayashi and Yasumasa Iwatani and Hiroshi Murakami}, title = {Monobodies with potent neutralizing activity against SARS-CoV-2 Delta and other variants of concern}, volume = {5}, number = {6}, elocation-id = {e202101322}, year = {2022}, doi = {10.26508/lsa.202101322}, publisher = {Life Science Alliance}, abstract = {Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are useful for patients{\textquoteright} 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 (KD \< 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.}, URL = {https://www.life-science-alliance.org/content/5/6/e202101322}, eprint = {https://www.life-science-alliance.org/content/5/6/e202101322.full.pdf}, journal = {Life Science Alliance} }