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

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.Impact statement:Potent and low-cost Nanosota-1 drugs block SARS-CoV-2 infections both in vitro and in vivo and act both preventively and therapeutically.

SUBMITTER: Ye G

PROVIDER: S-EPMC7685322 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Therapeutic antibodies under development for SARS‐CoV‐2

Project description:Abstract The world is experiencing one of the most difficult moments in history with COVID‐19, which has rapidly developed into a worldwide pandemic with a significant health and economic burden. Efforts to fight the virus, including prevention and treatment, have never stopped. However, no specific drugs or treatments have yet been found. Antibody drugs have never been absent in epidemics such as SARS, MERS, HIV, Ebola, and so on in the past two decades. At present, while research on the SARS‐CoV‐2 vaccine is in full swing, antibody drugs are also receiving widespread attention. Several antibody drugs have successfully entered clinical trials and achieved impressive therapeutic effects. Here, we summarize the therapeutic antibodies against SARS‐CoV‐2, as well as the research using ACE2 recombinant protein or ACE2‐Ig fusion protein. Several antibody drugs have successfully entered clinical trials and achieved impressive therapeutic effects. Due to the rapid progress in the field of therapeutic antibodies for COVID‐19 treatment, we summarized the neutralizing antibody drugs and fusion protein drugs that have attracted high attention at present, discussed the existing problems in the current application of antibodies drugs for COVID‐19, and prospected the future research direction in this field.

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SARS-CoV-2 detection using a nanobody-functionalized voltammetric device.

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