The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates.

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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Animals, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, COVID-19 Drug Treatment, HEK293 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Molecular, Pandemics, Protein Binding, Protein Conformation, Receptors, Virus, SARS-CoV-2, Single-Domain Antibodies, Spike Glycoprotein, Coronavirus
Elife
Date: Aug. 02, 2021
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