Viruses are typically detected with the help of specific biological antibodies. However, it is now also possible to produce synthetic receptor materials that can selectively bind viruses. For this process, a “chemical imprint” of the virus is created on the surface of polymer particles, which enables exclusive binding of a particular pathogen. Using super-resolution microscopy, a research team from Ulm has now successfully demonstrated, for the first time, how viruses dock on these molecularly imprinted receptor polymers. These highly selective artificial antibodies could potentially be useful for diagnostic identification of the novel coronavirus (SARS-CoV-2).
Scientists have already been able to produce polymer-based artificial antibodies that are capable of selectively binding certain viruses for a long time. In order to achieve this, a procedure known as “molecular imprinting” is applied to the surface of micro- or nanoparticles. “In molecular imprinting, the receptor material is imprinted with the specific ‘footprint’ of a virus. This ensures that no other virus can dock at this spot”, explains Professor Boris Mizaikoff, who is researching molecular imprinting with his team. The director of the Institute of Analytical and Bioanalytical Chemistry is the coordinator of a study that was published in the renowned journal Analytical Chemistry. What makes this study unique is that it was the first to successfully verify the rebinding of the virus to the artificial antibody not only chemically, but also visual visually.
Professor Jens Michaelis’s research team are specialists in super-resolution imaging of molecular structures. The director of the Institute of Biophysics used a special super-resolution imaging procedure known as STED microscopy for this study, which enables imaging with the highest spatial resolution. Using the “stimulated emission depletion” (STED) method, researchers were able to view individual virus particles with the help of special fluorescent dyes. The STED images have also shown that viruses only rarely bind to the non-imprinted polymer particles. “This is another aspect that we were able to visually verify for the first time thanks to this procedure”, says Michaelis.
Artificial antibodies from the chemistry lab
Molecular imprinting is a procedure with high biotechnological and pharmaceutical relevance for producing customised selective binding materials. “What makes this method unique is that we can use it to produce artificial antibodies in the chemistry lab, in many cases without even requiring infectious material”, says Mizaikoff. For the most part, it is sufficient to utilise a common protein from the virus casing as a ‘chemical print template’. Another advantage is that the procedure can be easily scaled, making it suitable for industrial-scale production as well.
The researchers from Ulm collaborated with the regional biotechnology company Labor Dr Merk & Kollegen GmbH in Ochsenhausen on this project. “The collaboration was very rewarding. The company supported us in addressing concrete application issues and exploring potential uses”, the researchers explain. Artificial antibodies are suitable for a wide range of analytical procedures. Thanks to selective detection, for example, molecularly imprinted polymers can be used to enrich and deplete viral substances. Molecular imprinting could open up valuable possibilities in the areas of diagnostics and detection, as well as in vaccine development and production. The corona pandemic is also forcing us to find new ways to detect SARS-CoV-2, and other viruses can be detected using these methods as well.
Microscopic images attest to the procedure’s functionality
What makes the Ulm study so important in scientific terms? “The field of research concerning molecularly imprinted materials continues to be controversial, in particular with respect to the control of the imprinting process and the quality of the receptor materials”, Boris Mizaikoff explains. It is therefore of utmost important that the complex procedure of surface modification can be understood from a rational perspective and can be reproduced. “I think that with this publication, we have been remarkably successful in providing this evidence”, the two scientists agree. Analytical Chemistry is published by the American Chemical Society and is considered the most prestigious journal in the field. The editors have dedicated the cover of this edition to the research project at Ulm University based on the topicality and importance of the subject. The study was funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) within the scope of the PROTSCAV II project.
Manuela Gast, Fanny Wondany, Bastian Raabe, Jens Michaelis, Harald Sobek and Boris Mizaikoff: Use of Super-Resolution Optical Microscopy to Reveal Direct Virus Binding at Hybrid Core−Shell Matrixes, in: Analytical Chemistry 2020, 92, 3050-3057; https://pubs.acs.org/doi/10.1021/acs.analchem.9b04328
Media contact: Andrea Weber-Tuckermann