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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
doi: https://doi.org/10.1101/2020.08.09.242867
Junwei Gai
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Linlin Ma
2Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
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Guanghui Li
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Min Zhu
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Peng Qiao
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Xiaofei Li
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Haiwei Zhang
3CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
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Yanmin Zhang
4Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing 211198, China
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Yadong Chen
4Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing 211198, China
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Weiwei Ji
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Hao Zhang
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Huanhuan Cao
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Xionghui Li
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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Rui Gong
3CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
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  • For correspondence: ykwan@novamab.com gongr@wh.iov.cn
Yakun Wan
1Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai 201318, China
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  • For correspondence: ykwan@novamab.com gongr@wh.iov.cn
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Abstract

The outbreak of COVID-19 has emerged as a global pandemic. The unprecedented scale and severity call for rapid development of effective prophylactics or therapeutics. 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, bat-SL-CoV-WIV1-RBD and SARS-CoV-1-RBD. Among the seven candidates, Nb11-59 exhibited the highest activity against authentic SARS-CoV-2 with ND50 of 0.55 μg/mL. Nb11-59 can be produced on a 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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Competing Interest Statement

All commercial rights from this paper belong to Shanghai Novamab Biopharmaceuticals Co., Ltd.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 14, 2020.
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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
bioRxiv 2020.08.09.242867; doi: https://doi.org/10.1101/2020.08.09.242867
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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
bioRxiv 2020.08.09.242867; doi: https://doi.org/10.1101/2020.08.09.242867

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