A1 Journal article (refereed)
Structure- and Interaction-Based Design of Anti-SARS-CoV-2 Aptamers (2022)

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., . . . Kichkailo, A. S. (2022). Structure- and Interaction-Based Design of Anti-SARS-CoV-2 Aptamers. Chemistry : A European Journal, 28(12), Article e202104481. https://doi.org/10.1002/chem.202104481

JYU authors or editors

Publication details

All authors or editors: 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.; et al.

Journal or series: Chemistry : A European Journal

ISSN: 0947-6539

eISSN: 1521-3765

Publication year: 2022

Publication date: 13/01/2022

Volume: 28

Issue number: 12

Article number: e202104481

Publisher: Wiley-VCH Verlag

Publication country: Germany

Publication language: English

DOI: https://doi.org/10.1002/chem.202104481

Publication open access: Other way freely accessible online

Publication channel open access:

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/79486

Abstract

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.

Keywords: SARS-CoV-2 virus; drug design; oligonucleotides; proteins; computational chemistry; molecular dynamics

Free keywords: aptamers; fragment molecular orbitals method; molecular dynamics; SARS-CoV-2; SAXS

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2022

Preliminary JUFO rating: 2