The pandemic has catalysed faster pharmaceutical processes. While vaccine and drug development typically takes 15 years, pharmaceutical companies began patient trials just a few months after the release of the SARS-CoV-2 RNA sequence. COVID-19 highlighted the need to study pathogens’ biology and develop new vaccines and therapies at unprecedented speed. Biosensors are valuable instruments for protein binding assays, which can be used to investigate novel mechanisms of action and help in the selection of the best vaccine and drug candidates.
Studies on SARS-CoV-2 receptor binding mechanisms allowed the design and implementation of therapeutic strategies to block the virus and boost immunity. A handful of monoclonal antibody (mAbs) treatments have already obtained emergency use authorisation (EUA) by the FDA and more are being tested. However, there are still a lot of unanswered questions, particularly concerning virus variants.
Typically, anti-COVID-19 drugs based on mAbs recognise only a particular region (epitope) of the viral spike protein. However, with the rapidly mutating virus, it became apparent that drugs have to interact with more than one part of the virus in order to be effective against the new variants. One strategy is to use mAb cocktails to recognise multiple virus epitopes. Additionally, other smaller protein binders – such as DARPins (designed ankyrin repeat proteins) and nanobodies – are also explored as drug candidates. These can be designed to bind more than one epitope at the same time. Earlier this year, a DARPin® treatment candidate started Phase 2a clinical trials. It was engineered to bind to the SARS-CoV-2 spike protein at three distinct locations and prevent viral entry into cells.
The current hurdle, when it comes to analysing binding of small proteins, is the detection limit. Most commonly used instruments rely on immobilising the smaller molecule (usually the antigen) and detecting the attachment of larger binding molecules (e.g., antibody). When it comes to measuring small protein binders this approach runs into compromised detection. That is why we are developing a new, label-free assay platform that detects changes in electrical charge during binding. Since it does not depend on the molecular weight or size of the binder, users can choose whether to immobilise antigens or antibodies (or other binders) on the sensor’s surface. This approach is better suited for the study of small protein binders, such as DARPins and nanobodies, and provides a fast measurement of binding kinetics constants.
Are you working on the current and future biomedical challenges? Which binders against COVID-19 are you studying and which problems are you facing? Let us know!
Harvard Health Publishing (2021). Treatments for COVID-19. Accessed 17 August 2021.
University of Cambridge (2021). Scientists identify 160 new drugs that could be repurposed against COVID-19. Accessed 17 August 2021.
Molecular Partners (2021). Molecular Partners announces first patient dosed in a Phase 2 clinical trial of ensovibep in COVID-19 patients. Accessed 17 August 2021.
Sasisekharan, R. (2021). "Preparing for the Future—Nanobodies for Covid-19?" New England Journal of Medicine, 384(16), 1568-1571.