Synthetic Nanobodies Offer Potential for Development of Inhalable COVID-19 Drugs

Synthetic nanobodies against the receptor binding domain (RBD) of SARS-CoV-2 hold particular promise for the development of inhalable drugs, which could offer a convenient treatment option for COVID-19.

Absolute Antibody, Ltd. (Oxford, UK) is partnering with the University of Zurich (Zürich, Switzerland) to offer recombinant engineered antibodies for COVID-19 diagnostics and therapeutic development. Under the partnership, the original nanobodies and newly engineered formats are now available to the global research community for use as serological controls and in COVID-19 therapeutic development.

Nanobodies are small antibody fragments that can reach previously inaccessible parts of the body due to their compact size. Researchers are exploring their potential as inhalable COVID-19 drugs, which would be easier to administer and reach patient’s lungs faster than other treatment formulations. The laboratory of Markus Seeger at the University of Zurich has developed a rapid in vitro selection platform to generate synthetic nanobodies, known as sybodies, against the receptor binding domain (RBD) of SARS-CoV-2. Within a two-week timeframe, the lab had identified more than 60 unique anti-RBD sybodies from combinatorial display libraries.

Further research showed that six of the sybodies bound SARS-CoV-2 spike protein with very high affinity, while five of those also inhibited ACE2, the host cell receptor to which SARS-CoV-2 binds to initiate the COVID-19 infection. Moreover, two of the sybodies can simultaneously bind the RBD, which could enable the construction of a polyvalent antiviral drug. The SARS-CoV-2 sybodies are therefore valuable tools for coronavirus research, diagnostics and therapeutic development, and the panel is now available to researchers worldwide.

Absolute Antibody has used antibody engineering to fuse the nanobodies to Fc domains in different species, isotypes and subtypes. For example, the anti-RBD binders are now available with human IgG1, IgG3, IgM and IgA domains for use as serological controls. These recombinant engineered antibodies extend the applications of the sybodies by varying effector function and permitting increased half-life in in vivo studies. In addition to the new synthetic antibodies, Absolute Antibody offers a variety of other engineered reagents for coronavirus research, including SARS-CoV-2 spike glycoprotein and nucleoprotein antibodies, ACE2 Fc fusion proteins, and anti-human immunoglobulin antibodies for use in diagnostic tests. The company is also supporting coronavirus research by providing antibody engineering and manufacturing services, such as the production of gram quantities of human antibodies sequenced from recovering COVID-19 patients.

“We are excited to partner with the Seeger lab to make their novel synthetic nanobodies more widely available to the research community,” said Dr. Michael Fiebig, Vice President Product Portfolio & Innovation at Absolute Antibody. “Combined with Absolute Antibody’s unique antibody engineering approach, we can harness even more potential from the nanobodies and help scientists worldwide fight against the COVID-19 pandemic.”

“The global research community has been working at unprecedented speeds to fight COVID-19,” said Dr. Markus Seeger, Professor at the Institute of Medical Microbiology of the University of Zurich. “By partnering with Absolute Antibody, we have extended the reach and applications of our new synthetic nanobodies, furthering their potential in the race to develop urgently required therapeutics.”

Related Links:
Absolute Antibody, Ltd.
University of Zurich