tetano
Editor, Senior Moderator
Chemistry
. 2022 Jan 13.
doi: 10.1002/chem.202104481. Online ahead of print.
Structure and Interaction Based Design of Anti-SARS-CoV-2 Aptamers
Vladimir Mironov[SUP] 1 [/SUP], Irina A Shchugoreva[SUP] 2 [/SUP], Polina V Artyushenko[SUP] 3 [/SUP], Dmitry Morozov[SUP] 4 [/SUP], Nicola Borbone[SUP] 5 [/SUP], Giorgia Oliviero[SUP] 6 [/SUP], Tatiana N Zamay[SUP] 7 [/SUP], Roman V Moryachkov[SUP] 8 [/SUP], Olga S Kolovskaya[SUP] 9 [/SUP], Kirill A Lukyanenko[SUP] 9 [/SUP], Yangling Song[SUP] 10 [/SUP], Iuliia A Merkuleva[SUP] 11 [/SUP], Vladimir N Zabluda[SUP] 12 [/SUP], Georgy Peters[SUP] 13 [/SUP], Lyudmila S Koroleva[SUP] 14 [/SUP], Dmitry V Veprintsev[SUP] 9 [/SUP], Yury E Glazyrin[SUP] 9 [/SUP], Ekaterina A Volosnikova[SUP] 11 [/SUP], Svetlana V Belenkaya[SUP] 11 [/SUP], Tatiana I Esina[SUP] 11 [/SUP], Anastasiya A Isaeva[SUP] 11 [/SUP], Valentina S Nesmeyanova[SUP] 11 [/SUP], Daniil V Shanshin[SUP] 11 [/SUP], Anna N Berlina[SUP] 15 [/SUP], Nadezhda S Komova[SUP] 15 [/SUP], Valery A Svetlichnyi[SUP] 16 [/SUP], Vladimir N Silnikov[SUP] 17 [/SUP], Dmitriy N Shcherbakov[SUP] 11 [/SUP], Galina S Zamay[SUP] 9 [/SUP], Sergey S Zamay[SUP] 9 [/SUP], Tatyana Smolyarova[SUP] 9 [/SUP], Elena P Tikhonova[SUP] 18 [/SUP], Kelvin H-C Chen[SUP] 19 [/SUP], U-Ser Jeng[SUP] 20 [/SUP], Gerolama Condorelli[SUP] 21 [/SUP], Vittorio de Franciscis[SUP] 22 [/SUP], Gerrit Groenhof[SUP] 23 [/SUP], Chaoyong Yang[SUP] 24 [/SUP], Alexander A Moskovsky[SUP] 1 [/SUP], Dmitri G Fedorov[SUP] 25 [/SUP], Felix N Tomilin[SUP] 26 [/SUP], Weihong Tan[SUP] 27 [/SUP], Yuri Alexeev[SUP] 28 [/SUP], Maxim V Berezovski[SUP] 29 [/SUP], Anna S Kichkailo[SUP] 30 [/SUP]
Affiliations
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: Aptamer, Coronavirus, Receptor Binding Domain, SARS-CoV-2, computational design.
. 2022 Jan 13.
doi: 10.1002/chem.202104481. Online ahead of print.
Structure and Interaction Based Design of Anti-SARS-CoV-2 Aptamers
Vladimir Mironov[SUP] 1 [/SUP], Irina A Shchugoreva[SUP] 2 [/SUP], Polina V Artyushenko[SUP] 3 [/SUP], Dmitry Morozov[SUP] 4 [/SUP], Nicola Borbone[SUP] 5 [/SUP], Giorgia Oliviero[SUP] 6 [/SUP], Tatiana N Zamay[SUP] 7 [/SUP], Roman V Moryachkov[SUP] 8 [/SUP], Olga S Kolovskaya[SUP] 9 [/SUP], Kirill A Lukyanenko[SUP] 9 [/SUP], Yangling Song[SUP] 10 [/SUP], Iuliia A Merkuleva[SUP] 11 [/SUP], Vladimir N Zabluda[SUP] 12 [/SUP], Georgy Peters[SUP] 13 [/SUP], Lyudmila S Koroleva[SUP] 14 [/SUP], Dmitry V Veprintsev[SUP] 9 [/SUP], Yury E Glazyrin[SUP] 9 [/SUP], Ekaterina A Volosnikova[SUP] 11 [/SUP], Svetlana V Belenkaya[SUP] 11 [/SUP], Tatiana I Esina[SUP] 11 [/SUP], Anastasiya A Isaeva[SUP] 11 [/SUP], Valentina S Nesmeyanova[SUP] 11 [/SUP], Daniil V Shanshin[SUP] 11 [/SUP], Anna N Berlina[SUP] 15 [/SUP], Nadezhda S Komova[SUP] 15 [/SUP], Valery A Svetlichnyi[SUP] 16 [/SUP], Vladimir N Silnikov[SUP] 17 [/SUP], Dmitriy N Shcherbakov[SUP] 11 [/SUP], Galina S Zamay[SUP] 9 [/SUP], Sergey S Zamay[SUP] 9 [/SUP], Tatyana Smolyarova[SUP] 9 [/SUP], Elena P Tikhonova[SUP] 18 [/SUP], Kelvin H-C Chen[SUP] 19 [/SUP], U-Ser Jeng[SUP] 20 [/SUP], Gerolama Condorelli[SUP] 21 [/SUP], Vittorio de Franciscis[SUP] 22 [/SUP], Gerrit Groenhof[SUP] 23 [/SUP], Chaoyong Yang[SUP] 24 [/SUP], Alexander A Moskovsky[SUP] 1 [/SUP], Dmitri G Fedorov[SUP] 25 [/SUP], Felix N Tomilin[SUP] 26 [/SUP], Weihong Tan[SUP] 27 [/SUP], Yuri Alexeev[SUP] 28 [/SUP], Maxim V Berezovski[SUP] 29 [/SUP], Anna S Kichkailo[SUP] 30 [/SUP]
Affiliations
- PMID: 35025110
- DOI: 10.1002/chem.202104481
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: Aptamer, Coronavirus, Receptor Binding Domain, SARS-CoV-2, computational design.