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 similar to 3000 times more tightly than ACE2 did and inhibited SARS-CoV-2 pseudovirus similar to 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.

Automated summary

Nanosota-1, a series of single-domain antibodies, has shown to effectively combat SARS-CoV-2 virus by binding to the receptor-binding domain, blocking viral receptor ACE2, and demonstrating preventive and therapeutic efficacy against live infection. Produced at high yields in bacteria and with exceptional thermostability, Nanosota-1 may potentially contribute to the battle against COVID-19 as an effective and inexpensive drug candidate.