Abstract
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.
Highlights
A genome-wide RNA profiling and differential analysis (GWRPD) of sequence variations in 1557 different variants of SARS-CoV-2 was performed. This analysis resulted in the identification of five sites with 98–99% conservation among all analyzed variants, as indicated by the red segments in the outer ring of the GWRPD map (Figure 1A)
Of primary interest is the homopurine/palindrome sequence indicated by the purple segment and font, located near the beginning of the genome within the coding region
Recent vaccines have proven effective in helping to counteract the SARS-CoV2 pandemic, variants have emerged, resulting in concern regarding the ability of the virus to develop resistance to available vaccines and antiviral drugs in development
Summary
The emergence of SARS-CoV-2 variants is cause for concern, because these may become resistant to current vaccines and antiviral drugs in development. 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. 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. Homopurine/homopyrimidine sequences within the viral genome were identified These sequences demonstrate appropriate target sites for antisense oligonucleotides and triplex-forming oligonucleotides.
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