Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e., nanobody), , from a camelid nanobody phage display library. Structural data showed that 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 () 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, demonstrated preventive and therapeutic efficacy against live SARS-CoV-2 infection in both hamster and mouse models. Unlike conventional antibodies, was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of c documented an excellent in vivo stability and a high tissue bioavailability. As effective and inexpensive drug candidates, may contribute to the battle against COVID-19.
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| http://dx.doi.org/10.7554/eLife.64815 | DOI Listing |
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