Pharmaceuticals (Oct 2021)

Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates

  • Hanah F. Huber,
  • Majid Jaberi-Douraki,
  • Sarah DeVader,
  • Cesar Aparicio-Lopez,
  • Juliet Nava-Chavez,
  • Xuan Xu,
  • Nuwan Indika Millagaha Gedara,
  • Natasha N. Gaudreault,
  • Robert K. Delong

DOI
https://doi.org/10.3390/ph14101012
Journal volume & issue
Vol. 14, no. 10
p. 1012

Abstract

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The emergence of SARS-CoV-2 variants is cause for concern, because these may become resistant to current vaccines and antiviral drugs in development. Current drugs target viral proteins, resulting in a critical need for RNA-targeted nanomedicines. To address this, a comparative analysis of SARS-CoV-2 variants was performed. Several highly conserved sites were identified, of which the most noteworthy is a partial homopurine palindrome site with >99% conservation within the coding region. This sequence was compared among recently emerged, highly infectious SARS-CoV-2 variants. Conservation of the site was maintained among these emerging variants, further contributing to its potential as a regulatory target site for SARS-CoV-2. RNAfold was used to predict the structures of the highly conserved sites, with some resulting structures being common among coronaviridae. An RNA-level regulatory map of the conserved regions of SARS-CoV-2 was produced based on the predicted structures, with each representing potential target sites for antisense oligonucleotides, triplex-forming oligomers, and aptamers. Additionally, homopurine/homopyrimidine sequences within the viral genome were identified. These sequences also demonstrate appropriate target sites for antisense oligonucleotides and triplex-forming oligonucleotides. An experimental strategy to investigate these is summarized along with potential nanoparticle types for delivery, and the advantages and disadvantages of each are discussed.

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