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The Development of a Novel Nanobody Therapeutic for SARS-CoV-2
Preprint   Open access

The Development of a Novel Nanobody Therapeutic for SARS-CoV-2

Gang Ye, Joseph P Gallant, Christopher Massey, Ke Shi, Wanbo Tai, Jian Zheng, Abby E Odle, Molly A Vickers, Jian Shang, Yushun Wan, …
bioRxiv: the preprint server for biology
Cold Spring Harbor Laboratory
11/17/2020
DOI: 10.1101/2020.11.17.386532
PMID: 33236012
url
https://doi.org/10.1101/2020.11.17.386532View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a novel 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 out viral receptor ACE2. The lead drug possessing an Fc tag ( Nanosota-1C-Fc ) bound to SARS-CoV-2 RBD with a K d of 15.7picomolar (∼3000 times more tightly than ACE2 did) and inhibited SARS-CoV-2 infection with an ND 50 of 0.16microgram/milliliter (∼6000 times more potently than ACE2 did). Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy in hamsters subjected to SARS-CoV-2 infection. Unlike conventional antibody drugs, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-F c documented a greater than 10-day in vivo half-life efficacy and high tissue bioavailability. Nanosota-1C-Fc is a potentially effective and realistic solution to the COVID-19 pandemic.

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