1/18/2023 0 Comments Rbd cd completo downloadThe lead nanobody monomers are hyperthermostable, bind the RBD with low-picomolar affinity and neutralize the virus at a concentration of 0.2–0.7 micrograms per liter (IC99 +).Alpaca immune libraries yielded 45 VHHs (of 22 sequence classes) that target two epitopes of the SARS-CoV-2 receptor-binding domain (RBD) and block infection.This study revealed highly potent therapeutic nanobodies/single-domain (VHH) antibodies that neutralize SARS-CoV-2 and its emerging immune-escape mutants. ![]() SYNOPSISĮffective treatment options for SARS-CoV-2 infections/COVID-19 are still sparse. Such “fold-promoting” nanobodies may allow for simplified production of vaccines and their adaptation to viral escape-mutations. ![]() We further discovered VHH antibodies that enforce native folding of the RBD in the E. coli cytosol, where its folding normally fails. ![]() We also demonstrate neutralization of the Beta strain at low-picomolar VHH concentrations. We constructed nanobody tandems and identified nanobody monomers that tolerate the K417N/T, E484K, N501Y, and L452R immune-escape mutations found in the Alpha, Beta, Gamma, Epsilon, Iota, and Delta/Kappa lineages. The best VHH trimers neutralize even at 40 ng per liter. 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. These include nanobodies that can withstand 95☌. Using alpaca immune libraries against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein, we isolated 45 infection-blocking VHH antibodies. ![]() Single-domain (VHH) antibodies (also called nanobodies) provide an alternative suitable for microbial production. However, their production in mammalian cells is not scalable to meet the global demand. Monoclonal anti-SARS-CoV-2 immunoglobulins represent a treatment option for COVID-19.
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