COVID 19 research projects at BIO

SARS CoV2 Serology

In a collaborative effort with the University Hospital Zürich, the Schertler group is spearheading efforts to establish a platform for large-scale screening of antibody profiles against SARS CoV2 antigens. PSI is producing a number of SARS CoV2 antigens, including all structural SARS CoV2 proteins as well as the main host receptor, which are then used by team of Adriano Aguzzi in a  population-based high-throughput screening to investigate the antibody response against these antigens among COVID 19 survivors as well as within the general population. This information will then be used to identify (1) the time point when CoV2 established itself in Switzerland, (2) the true prevalence of subclinical infection, and discover (3) any extrapulmonary CoV2 pathogenicity (e.g. endocarditis, hepatitis, gastroenteritis, meningitis etc.), (4) specific immune responses predictive of disease severity, (5) pulmotoxic responses triggering cytokine storms in late disease, and (6) late-onset sequelae due to e.g. viral dormancy/reactivation and persistence in sanctuary organs.

Structure-based SARS CoV2 Antidote development

The Serology study with the Aguzzi lab from the University Hospital Zürich will result in the identification and production of anti-SARS CoV2 antibodies with therapeutic potential. In order to understand their interaction with the viral antigens the Schertler group is currently producing all structural viral proteins in quantities and qualities, which are sufficient for structure determination with X-ray crystallography or single particle Electron Microscopy. They will then deduce the structure of these protein alone and in complex with the promising antibodies from the serology screen. In a joint effort with the research groups of Ana-Nicoleta Bondar (Free University of Berlin, Germany) and Abbas Ourmazd (University of Wisconsin-Milwaukee, USA) advanced analysis methods will be used to characterize the conformational heterogeneity of antigens from CoV2 and other Coronaviruses. This will allow the researchers to deduce whether neutralizing antibodies induce or stabilize specific conformations in viral proteins. This information that can be used to speed up and optimize the development of new therapeutic approaches.

Virus Capsids

Roger Benoit at the Laboratory for Nanoscale Biology (LNB) is specialized in structure-based protein engineering. Virus capsids are symmetric shells enclosing the viral genome. They are typically built from multiple copies of one or a few protein components. The capsids of many viruses can be produced alone, without viral genetic material. Their component proteins can be genetically fused to peptidic or proteinaceous epitopes of any virus, making them useful as self-assembling immunization agents or as tools for the development of novel virus detection methods. The team of Roger Benoit has developed special protein-protein linkers to produce nanoparticles that display SARS-2-CoV-19 epitopes at specific angles and spacings, to optimize immunogenicity.

For further information, please visit also the Molecular Biology site at PSD.

Figure: PET images of inflamed (A) and healthy (B) lungs of mice injected with 18F-AzaFol, which accumulates in folate receptor expressing macrophages.

Imaging Lung Inflammation using PET: The Use of 18F-AzaFol and beyond

The Center for Radiopharmaceutical Sciences (CRS) focuses on the development of new radiopharmaceuticals for positron emission tomography (PET) and other applications in nuclear medicine. Researchers at CRS have previously developed an 18F-based PET tracer (18F-AzaFol) for targeting the folate receptor, which is expressed on tumor cells, but also on activated macrophages involved in inflammatory processes. In a recent clinical study, 18F-AzaFol was investigated regarding its in vivo properties for folate-receptor targeting and assessed with respect to its safety profile in patients (NCT03242993).

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