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Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies

EMBO J. 2021-08; 
Thomas Güttler, Metin Aksu, Antje Dickmanns, Kim M Stegmann, Kathrin Gregor, Renate Rees, Waltraud Taxer, Oleh Rymarenko, Jürgen Schünemann, Christian Dienemann, Philip Gunkel, Bianka Mussil, Jens Krull, Ulrike Teichmann, Uwe Groß, Volker C Cordes, Matthias Dobbelstein, Dirk Görlich
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Recombinant Proteins biotinylated nanobodies were immobilized, incubated with 20, 6.66, and 2.22 nM RBD wt (Z03479, GenScript) Get A Quote


Monoclonal anti-SARS-CoV-2 immunoglobulins represent a treatment option for COVID-19. However, their production in mammalian cells is not scalable to meet the global demand. Single-domain (VHH) antibodies (also called nanobodies) provide an alternative suitable for microbial production. Using alpaca immune libraries against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein, we isolated 45 infection-blocking VHH antibodies. These include nanobodies that can withstand 95°C. The most effective VHH antibody neutralizes SARS-CoV-2 at 17-50 pM concentration (0.2-0.7 µg per liter), binds the open and closed states of the Spike, and shows a tight RBD interaction in the X-ray and cryo-EM structures. ... More


COVID-19, Coronaviridae, SARS-CoV-2, VHH antibody, nanobody