An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo–electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.
Source: ScienceNOW - Category: Science Authors: Schoof, M., Faust, B., Saunders, R. A., Sangwan, S., Rezelj, V., Hoppe, N., Boone, M., Billesbolle, C. B., Puchades, C., Azumaya, C. M., Kratochvil, H. T., Zimanyi, M., Deshpande, I., Liang, J., Dickinson, S., Nguyen, H. C., Chio, C. M., Merz, G. E., Thom Tags: Biochemistry, Microbiology reports Source Type: news
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