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A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential.
Gai, Junwei; Ma, Linlin; Li, Guanghui; Zhu, Min; Qiao, Peng; Li, Xiaofei; Zhang, Haiwei; Zhang, Yanmin; Chen, Yadong; Ji, Weiwei; Zhang, Hao; Cao, Huanhuan; Li, Xionghui; Gong, Rui; Wan, Yakun.
  • Gai J; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Ma L; Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health Sciences Shanghai China.
  • Li G; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Zhu M; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Qiao P; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Li X; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Zhang H; CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science Chinese Academy of Sciences Wuhan China.
  • Zhang Y; Laboratory of Molecular Design and Drug Discovery, School of Science China Pharmaceutical University Nanjing China.
  • Chen Y; Laboratory of Molecular Design and Drug Discovery, School of Science China Pharmaceutical University Nanjing China.
  • Ji W; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Zhang H; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Cao H; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Li X; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
  • Gong R; CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science Chinese Academy of Sciences Wuhan China.
  • Wan Y; Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China.
MedComm (2020) ; 2(1): 101-113, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1121801
Preprint
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ABSTRACT
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 µg/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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Full text: Available Collection: International databases Database: MEDLINE Topics: Variants Language: English Journal: MedComm (2020) Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Topics: Variants Language: English Journal: MedComm (2020) Year: 2021 Document Type: Article