期刊
MEDCOMM
卷 2, 期 1, 页码 101-113出版社
WILEY
DOI: 10.1002/mco2.60
关键词
large-scale production; nanobody; nebulization; neutralizing activity; SARS-CoV-2
资金
- NationalNatural Science Foundation of China [81902052]
- Shanghai Sailing Program [20YF1434300]
- Natural Science Foundation of Hubei Province ofChina [2019CFA076]
The study identified a nanobody, Nb11-59, with high neutralizing activity against SARS-CoV-2 and the ability to be produced at large scale with high purity. Nb11-59 showed good neutralizing effects against authentic virus and remained stable even after nebulization.
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 (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 mu 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.
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