14th International Conference on Biology and Synchrotron Radiation

Role of BioSAXS in the fight against coronavirus: from viral protein characterization to vaccine development.

Not scheduled

20m

Palaestra et Odeum & AF Borgen (Lund)

Speaker

Clement Blanchet (EMBL Hamburg)

Description

Biological small angle scattering is a key method in biophysics and structural biology. It provides information on the size, shape, flexibility, and oligomeric composition of biological macromolecules. SAXS measure the sample directly in solution, in a quasi-native environment and is complementary to high resolution methods such as X-ray crystallography and Cryo-EM. In particular, structural changes triggered by modifications of the sample conditions (change in temperature, pH, salt or ligand concentration) can be monitored in screening or time-resolved experiments.
BioSAXS contributed to the description of the SARS-CoV-2 virus and to the development of vaccine and potential drugs. Its role in the fight against coronavirus will be illustrated with several projects carried out on the P12 beamline of EMBL Hamburg. SAXS was employed, for example, to characterize the topology of proteins involved in RNA replication for different coronavirus1. SAXS helped characterize the spike protein and its interaction with synthetic nanobodies that could neutralize the virus2. Beyond the study of the viral components, SAXS is also used to characterize and design the lipid nanoparticules that carries messenger RNA in new generation vaccine3,4,5.

1. Krichel, B., Bylapudi, G., Schmidt, C., Blanchet, C., Schubert, R., Brings, L., ... & Uetrecht, C. (2021). Hallmarks of Alpha-and Betacoronavirus non-structural protein 7+ 8 complexes. Science Advances, 7(10), eabf1004.
2. Custódio, T. F., Das, H., Sheward, D. J., Hanke, L., Pazicky, S., Pieprzyk, J., ... & Löw, C. (2020). Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2. Nature communications, 11(1), 1-11.
3. Uebbing, L., Ziller, A., Siewert, C., Schroer, M. A., Blanchet, C. E., Svergun, D. I., ... & Langguth, P. (2020). Investigation of pH-Responsiveness inside Lipid Nanoparticles for Parenteral mRNA Application Using Small-Angle X-ray Scattering. Langmuir, 36(44), 13331-13341.
4. Nogueira, S. S., Schlegel, A., Maxeiner, K., Weber, B., Barz, M., Schroer, M. A., ... & Haas, H. (2020). Polysarcosine-functionalized lipid nanoparticles for therapeutic mRNA delivery. ACS Applied Nano Materials, 3(11), 10634-10645.
5. Siewert, C. D., Haas, H., Cornet, V., Nogueira, S. S., Nawroth, T., Uebbing, L., ... & Langguth, P. (2020). Hybrid biopolymer and lipid nanoparticles with improved transfection efficacy for mRNA. Cells, 9(9), 2034.