Structure- and Interaction-Based Design of Anti-SARS-CoV-2 Aptamers.
Chemistry
; 28(12): e202104481, 2022 Feb 24.
Article
in English
| MEDLINE | ID: covidwho-1620111
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 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Aptamers, Nucleotide
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
/
Systematic review/Meta Analysis
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Chemistry
Journal subject:
Chemistry
Year:
2022
Document Type:
Article
Affiliation country:
Chem.202104481
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