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SARS-CoV-2 proteins structural studies using synchrotron radiation

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Abstract

In the process of the development of structural biology, both the size and the complexity of the determined macromolecular structures have grown significantly. As a result, the range of application areas for the results of structural studies of biological macromolecules has expanded. Significant progress in the development of structural biology methods has been largely achieved through the use of synchrotron radiation. Modern sources of synchrotron radiation allow to conduct high-performance structural studies with high temporal and spatial resolution. Thus, modern techniques make it possible to obtain not only static structures, but also to study dynamic processes, which play a key role in understanding biological mechanisms. One of the key directions in the development of structural research is the drug design based on the structures of biomolecules. Synchrotron radiation offers insights into the three-dimensional time-resolved structure of individual viral proteins and their complexes at atomic resolution. The rapid and accurate determination of protein structures is crucial for understanding viral pathogenicity and designing targeted therapeutics. Through the application of experimental techniques, including X-ray crystallography and small-angle X-ray scattering (SAXS), it is possible to elucidate the structural details of SARS-CoV-2 virion containing 4 structural, 16 nonstructural proteins (nsp), and several accessory proteins. The most studied potential targets for vaccines and drugs are the structural spike (S) protein, which is responsible for entering the host cell, as well as nonstructural proteins essential for replication and transcription, such as main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp). This article provides a brief overview of structural analysis techniques, with focus on synchrotron radiation-based methods applied to the analysis of SARS-CoV-2 proteins.

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Funding

This study was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement №075-15-2021-1355).

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All authors contributed to the study conception and design. The first draft of the manuscript was written by M.K., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. A.R. led the work and reviewed the manuscript.

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Correspondence to Maksim Kosenko.

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Kosenko, M., Onkhonova, G., Susloparov, I. et al. SARS-CoV-2 proteins structural studies using synchrotron radiation. Biophys Rev 15, 1185–1194 (2023). https://doi.org/10.1007/s12551-023-01153-7

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  • DOI: https://doi.org/10.1007/s12551-023-01153-7

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