Gai J, Ma L, Li G, Zhu M, Qiao P, Li X, Zhang H, Zhang Y, Chen Y, Ji W, Zhang H, Cao H, Li X, Gong R, Wan Y

The coronavirus disease 2019 (COVID-19) pandemic has become a serious burden on global public health. Although therapeutic drugs against COVID-19 have been used in many countries, their efficacy is still limited. We here reported nanobody (Nb) phage display libraries derived from four camels immunized with the SARS-CoV-2 spike receptor-binding domain ...

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(RBD), from which 381 Nbs were identified to recognize SARS-CoV-2-RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin-converting enzyme 2 (ACE2) with SARS-CoV-2-RBD variants and two Nbs blocked the interaction of human ACE2 with bat-SL-CoV-WIV1-RBD and SARS-CoV-1-RBD. Among these candidates, Nb11-59 exhibited the highest activity against authentic SARS-CoV-2 with 50% neutralizing dose (ND50) of 0.55 ?g/ml. Nb11-59 can be produced on large scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11-59 might be a promising prophylactic and therapeutic molecule against COVID-19, especially through inhalation delivery.

Date: Mar. 01, 2021

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