A potent neutralizing nanobody against SARS‐CoV‐2 with inhaled delivery potential
Junwei Gai,
Linlin Ma,
Guanghui Li,
Min Zhu,
Peng Qiao,
Xiaofei Li,
Haiwei Zhang,
Yanmin Zhang,
Yadong Chen,
Weiwei Ji,
Hao Zhang,
Huanhuan Cao,
Xionghui Li,
Rui Gong,
Yakun Wan
Affiliations
Junwei Gai
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Linlin Ma
Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health Sciences Shanghai China
Guanghui Li
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Min Zhu
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Peng Qiao
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Xiaofei Li
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Haiwei Zhang
CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan China
Yanmin Zhang
Laboratory of Molecular Design and Drug Discovery, School of Science China Pharmaceutical University Nanjing China
Yadong Chen
Laboratory of Molecular Design and Drug Discovery, School of Science China Pharmaceutical University Nanjing China
Weiwei Ji
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Hao Zhang
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Huanhuan Cao
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Xionghui Li
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
Rui Gong
CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan China
Yakun Wan
Shanghai Novamab Biopharmaceuticals Co., Ltd Shanghai China
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.
