Structure and Interaction Based Design of Anti-SARS-CoV-2 Aptamers

Mironov, V.; Shchugoreva, I.A.; Artyushenko, P.V.; Morozov, D.; Borbone, N.; Oliviero, G.; Zamay, T.N.; Moryachkov, R.V.; Kolovskaya, O.S.; Lukyanenko, K.A.; Song, Y.; Merkuleva, I.A.; Zabluda, V.N.; Peters, G.; Koroleva, L.S.; Veprintsev, D.V.; Glazyrin, Y.E.; Volosnikova, E.A.; Belenkaya, S.V.; Esina, T.I.; Isaeva, A.A.; Nesmeyanova, V.S.; Shanshin, D.V.; Berlina, A.N.; Komova, N.S.; Svetlichnyi, V.A.; Silnikov, V.N.; Shcherbakov, D.N.; Zamay, G.S.; Zamay, S.S.; Smolyarova, T.; Tikhonova, E.P.; Chen Kelvin, H.C.; Jeng, U.; Condorelli, G.; de Franciscis, V.; Groenhof, G.; Yang, C.; Moskovsky, A.A.; Fedorov, D.G.; Tomilin, F.N.; Tan, W.; Alexeev, Y.; Berezovski, M.V.; Kichkailo, A.S.

Авторы: Mironov Vladimir, Shchugoreva Irina A., Artyushenko Polina V., Morozov Dmitry, Borbone Nicola, Oliviero Giorgia, Zamay Tatiana N., Moryachkov Roman V., Kolovskaya Olga S., Lukyanenko Kirill A., Song Yangling, Merkuleva Iuliia A., Zabluda Vladimir N., Peters Georgy, Koroleva Lyudmila S., Veprintsev Dmitry V., Glazyrin Yury E., Volosnikova Ekaterina A., Belenkaya Svetlana V., Esina Tatiana I., Isaeva Anastasiya A., Nesmeyanova Valentina S., Shanshin Daniil V., Berlina Anna N., Komova Nadezhda S., Svetlichnyi Valery A., Silnikov Vladimir N., Shcherbakov Dmitriy N., Zamay Galina S., Zamay Sergey S., Smolyarova Tatyana, Tikhonova Elena P., Chen Kelvin H.C., Jeng U-Ser, Condorelli Gerolama, de Franciscis Vittorio, Groenhof Gerrit, Yang Chaoyong, Moskovsky Alexander A., Fedorov Dmitri G., Tomilin Felix N., Tan Weihong, Alexeev Yuri, Berezovski Maxim V., Kichkailo Anna S.
Журнал: Chemistry - A European Journal
Год издания: 2022
Издательство: John Wiley & Sons Ltd.
Местоположение издательства: United Kingdom
DOI: 10.1002/chem.202104481
Аннотация: Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design. The new approach combines multiple steps: (1) Molecular design, based on screening in a DNA aptamer library and directed mutagenesis to fit the protein tertiary structure; (2) 3D molecular modeling of the target; (3) Molecular docking of an aptamer with the protein; (4) Molecular dynamics (MD) simulations of the complexes; (5) Quantum-mechanical (QM) evaluation of the interactions between aptamer and target with further analysis; (6) Experimental verification at each cycle for structure and binding affinity using small-angle X-ray scattering, cytometry, and fluorescence polarization. Using a new iterative design procedure, Interaction Based Drug Design (SIBDD), a highly specific aptamer to the receptor-binding domain of the SARS-CoV-2 spike protein, was developed and validated. The SIBDD approach enhances speed of the high-affinity aptamers development from scratch, using a target protein structure. The method could be used to improve existing aptamers for stronger binding. This approach brings to an advanced level the development of novel affinity probes, functional nucleic acids. It offers a blueprint for the straightforward design of targeting molecules for new pathogen agents and emerging variants.
Добавил в систему: Миронов Владимир Андреевич

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Structure and Interaction Based Design of Anti-SARS-CoV-2 Aptamersстатья