Innovative Antibody Therapies Against COVID-19

The goal is to develop ultra-potent binding domains (SBDs) and antibodies to neutralise the new coronavirus (SARS-CoV-2), which causes the respiratory disease COVID-19. The trimeric coronavirus “spike” glycoprotein on the virus surface is responsible for the virus entering the cell and is therefore the sole target for neutralising antibodies to develop vaccines or therapeutics. Using the existing platform technologies, highly neutralising SBDs (in the form of nanobodies and human HCAbs) will be generated against the "spike" protein of SARS-CoV-2. It is anticipated that the neutralisation capacity can be increased even further by generating multi-specific antibodies and binding domains. So good SDB blockers will be linked to make bi- or tri-valent molecules that bind multiple epitopes of the “spike” protein.

This innovative approach is expected to enhance potency by 1) increasing avidity and stability of binding, 2) better blocking spike binding to its cellular receptor and/or 3) more effectively preventing spike conformational change required for fusion. The mode of action will be determined by structural and virological determinations. Promising candidates will be tested for proof-of-concept preclinical efficacy and safety protection in animal models. The screening of the SBDs for their antiviral activity will provide insight into the weaknesses of SARS-CoV-2 and contribute to the development of prophylactics and therapeutics. In addition, it is expected that the innovative strategy for the optimisation of “biologicals” (multi-valence) will be a starting point for the development of a more general intervention strategy for coronaviruses, thereby contributing to international public health precaution and response to future disease outbreaks.