1. The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates
- Author
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Jian Shang, Joseph P. Gallant, Jian Zheng, Fang Li, Christopher Massey, Molly A. Vickers, Ke Shi, Aaron M. LeBeau, Lanying Du, Yushun Wan, Abby E. Odle, Stanley Perlman, Hideki Aihara, Wanbo Tai, and Gang Ye
- Subjects
Drug ,Phage display ,QH301-705.5 ,Science ,media_common.quotation_subject ,ACE2 ,Hamster ,spike protein receptor-binding domain ,Plasma protein binding ,General Biochemistry, Genetics and Molecular Biology ,Virus ,crystal structures ,In vivo ,Biology (General) ,single-chain antibody from camelids ,media_common ,General Immunology and Microbiology ,biology ,Chemistry ,General Neuroscience ,COVID-19 ,General Medicine ,Virology ,Viral Receptor ,virus neutralization ,biology.protein ,Medicine ,Antibody - Abstract
Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking viral receptor angiotensin-converting enzyme 2 (ACE2). The lead drug candidate possessing an Fc tag (Nanosota-1C-Fc) bound to SARS-CoV-2 RBD ~3000 times more tightly than ACE2 did and inhibited SARS-CoV-2 pseudovirus ~160 times more efficiently than ACE2 did. Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy against live SARS-CoV-2 infection in both hamster and mouse models. Unlike conventional antibodies, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-Fc documented an excellent in vivo stability and a high tissue bioavailability. As effective and inexpensive drug candidates, Nanosota-1 may contribute to the battle against COVID-19.
- Published
- 2021
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