The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.908 Diseases
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2021
• Mô tả vật lý: Size: Article No. e64815 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 259649
• Chủ đề: 1. 60 applied life sciences; 2. Ace2; 3. Animal model; 4. Covid-19; 5. Crystal structures; 6. Drug pharmacokinetics; 7. Microbiology and infectious disease; 8. Single-chain antibody from camelids; 9. Spike protein receptor-binding domain; 10. Virus neutralization

Tóm tắt

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.