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

Journal Article · · Chemistry - A European Journal
 [1];  [2];  [2];  [3];  [4];  [4];  [5];  [6];  [7];  [8];  [9];  [10];  [11];  [12];  [13];  [14];  [7];  [10];  [10];  [10] more »;  [10];  [10];  [10];  [15];  [15];  [16];  [13];  [17];  [7];  [14];  [18];  [5];  [19];  [20];  [21];  [22];  [3];  [23];  [24];  [25];  [26];  [27];  [28];  [29]; ORCiD logo [7] « less
  1. Lomonosov Moscow State Univ., Moscow (Russian Federation); Kyungpook National Univ., Daegu (Korea, Republic of)
  2. Russian Academy of Sciences (RAS), Krasnoyarsk (Russian Federation); Siberian Federal Univ., Krasnoyarsk (Russian Federation); Krasnoyarsk State Medical Univ. (Russian Federation)
  3. Univ. of Jyvaskyla (Finland)
  4. Univ. of Naples Federico II (Italy)
  5. Krasnoyarsk State Medical Univ. (Russian Federation)
  6. Russian Academy of Sciences (RAS), Krasnoyarsk (Russian Federation); Kirensky Institute of Physics, Krasnoyarsk (Russia)
  7. Russian Academy of Sciences (RAS), Krasnoyarsk (Russian Federation); Krasnoyarsk State Medical Univ. (Russian Federation)
  8. Russian Academy of Sciences (RAS), Krasnoyarsk (Russian Federation); Krasnoyarsk State Medical Univ. (Russian Federation); Siberian Federal Univ., Krasnoyarsk (Russian Federation)
  9. Xiamen Univ. (China)
  10. State Research Center of Virology and Biotechnology (VECTOR), Koltsovo (Russian Federation)
  11. Kirensky Institute of Physics, Krasnoyarsk (Russia)
  12. National Research Centre (NRC), Moscow (Russian Federation)
  13. Russian Academy of Sciences (RAS), Novosibirsk (Russian Federation)
  14. Russian Academy of Sciences (RAS), Krasnoyarsk (Russian Federation)
  15. Russian Academy of Sciences (RAS), Moscow (Russian Federation)
  16. Tomsk State Univ. (Russian Federation)
  17. State Research Center of Virology and Biotechnology (VECTOR), Koltsovo (Russian Federation); Altai State Univ., Barnaul (Russian Federation)
  18. Russian Academy of Sciences (RAS), Krasnoyarsk (Russian Federation); Siberian Federal Univ., Krasnoyarsk (Russian Federation)
  19. National Pingtung Univ. (Taiwan)
  20. National Synchrotron Radiation Research Center, Hsinchu (Taiwan); National Tsing Hua Univ., Hsinchu (Taiwan)
  21. Univ. of Naples Federico II (Italy); Istituto Neurologico Mediterraneo Pozzilli (Italy)
  22. National Research Council (CNR), Milan (Italy)
  23. Xiamen Univ. (China); Shanghai Jiao Tong Univ. (China)
  24. Lomonosov Moscow State Univ., Moscow (Russian Federation)
  25. National Inst. of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan)
  26. Siberian Federal Univ., Krasnoyarsk (Russian Federation); Kirensky Institute of Physics, Krasnoyarsk (Russia)
  27. Shanghai Jiao Tong Univ. (China); Hunan Univ., Changsha (China)
  28. Argonne National Lab. (ANL), Argonne, IL (United States)
  29. Univ. of Ottawa, ON (Canada)
+ Show Author Affiliations

Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. In this study, we aim 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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC); European Union (EU); Russian Foundation for Basic Research; Ministry of Science and Higher Education of Russian Federation; Italian Ministry of Education; Canadian Institutes of Health Research (CIHR); Russian Science Foundation
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1869968
Journal Information:
Chemistry - A European Journal, Journal Name: Chemistry - A European Journal Journal Issue: 12 Vol. 28; ISSN 0947-6539
Publisher:
ChemPubSoc EuropeCopyright Statement
Country of Publication:
United States
Language:
English

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60 APPLIED LIFE SCIENCES
SARS-CoV-2
SAXS
aptamers
fragment molecular orbitals method
molecular dynamics