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?:abstract
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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-Fc 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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?:doi
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?:doi
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10.1101/2020.11.17.386532
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document_parses/pdf_json/fb8f9dbe79d3562f069112a3c0cec3df43c9e1f9.json; document_parses/pdf_json/f341b7577481489ec7124c6830980f28896c5a44.json
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document_parses/pmc_json/PMC7685322.xml.json
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?:source
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BioRxiv; Medline; PMC; WHO
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?:title
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The Development of a Novel Nanobody Therapeutic for SARS-CoV-2
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