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

UNLABELLED

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 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 ( ) bound to SARS-CoV-2 RBD with a K of 15.7picomolar (∼3000 times more tightly than ACE2 did) and inhibited SARS-CoV-2 infection with an ND of 0.16microgram/milliliter (∼6000 times more potently than ACE2 did). Administered at a single dose, demonstrated preventive and therapeutic efficacy in hamsters subjected to SARS-CoV-2 infection. Unlike conventional antibody drugs, was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of c documented a greater than 10-day half-life efficacy and high tissue bioavailability. is a potentially effective and realistic solution to the COVID-19 pandemic.

IMPACT STATEMENT

Potent and low-cost drugs block SARS-CoV-2 infections both and and act both preventively and therapeutically.