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 by using small-angle X-ray scattering, cytometry, and fluorescence polarization

By using a new iterative design procedure, structure- and 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.


Vladimir Mironov, Irina A. Shchugoreva, Polina V. Artyushenko, Dmitry Morozov, Nicola Borbone,  Giorgia Oliviero, Tatiana N. Zamay, Roman V. Moryachkov, Olga S. Kolovskaya, Kirill A. Lukyanenko, Yanling Song, Iuliia A. Merkuleva, Vladimir N. Zabluda, Georgy Peters,  Lyudmila S. Koroleva, Dmitry V. Veprintsev,  Yury E. Glazyrin, Ekaterina A. Volosnikova, Svetlana V. Belenkaya, Tatiana I. Esina, Anastasiya A. Isaeva, Valentina S. Nesmeyanova, Daniil V. Shanshin, Anna N. Berlina, Nadezhda S. Komova, Valery A. Svetlichnyi, Vladimir N. Silnikov, Dmitriy N. Shcherbakov, Galina S. Zamay, Sergey S. Zamay, Tatyana Smolyarova, Elena P. Tikhonova,  Kelvin H.-C. Chen,  U-Ser Jeng, Gerolama Condorelli, Vittorio de Franciscis, Gerrit Groenhof, Chaoyong Yang, Alexander A. Moskovsky, Dmitri G. Fedorov, Felix N. Tomilin, Weihong Tan, Yuri Alexeev, Maxim V. Berezovski, Anna S. Kichkailo (2022):
Structure- and Interaction-Based Design of Anti-SARS-CoV-2 Aptamers.
Chemistry – A European Journal 24(12):e202104481

About the author

Stian works in School of Computer Science, at the University of Manchester in Carole Goble‘s eScience Lab as a technical software architect and researcher. In addition to BioExcel, Stian’s involvements include Open PHACTS (pharmacological data warehouse), Common Workflow Language (CWL), Apache Taverna (scientific workflow system), Linked Data and identifiers, research objects (open science) and digital preservation, myExperiment (sharing scientific workflows), provenance (where did things come from and who did it) and annotations (who said what). orcid.org/0000-0001-9842-9718