DAPTEV: Deep aptamer evolutionary modelling for COVID-19 drug design

PLoS Comput Biol. 2023 Jul 5;19(7):e1010774. doi: 10.1371/journal.pcbi.1010774. eCollection 2023 Jul.

Abstract

Typical drug discovery and development processes are costly, time consuming and often biased by expert opinion. Aptamers are short, single-stranded oligonucleotides (RNA/DNA) that bind to target proteins and other types of biomolecules. Compared with small-molecule drugs, aptamers can bind to their targets with high affinity (binding strength) and specificity (uniquely interacting with the target only). The conventional development process for aptamers utilizes a manual process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX), which is costly, slow, dependent on library choice and often produces aptamers that are not optimized. To address these challenges, in this research, we create an intelligent approach, named DAPTEV, for generating and evolving aptamer sequences to support aptamer-based drug discovery and development. Using the COVID-19 spike protein as a target, our computational results suggest that DAPTEV is able to produce structurally complex aptamers with strong binding affinities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide* / chemistry
  • COVID-19*
  • Drug Design
  • Humans
  • Ligands
  • RNA
  • SELEX Aptamer Technique / methods

Substances

  • Aptamers, Nucleotide
  • RNA
  • Ligands

Grants and funding

This work was supported by the AI for Design Challenge Program from the National Research Council Canada (AI4D-108-2 to YL), the Discovery Grant Program from the National Sciences and Engineering Research Council of Canada (RGPIN 2021-03879 to YL), Ontario Graduate Scholarships (to CA), Schmidt Science Fellows in partnership with the Rhodes Trust and the HHMI Hanna H. Gray Fellows Program (to KK). MCC is an employee of the National Research Council Canada and, therefore, receives a salary. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.