Development of a highly stable, active small interfering RNA with broad activity against SARS-CoV viruses.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8109699 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9096 (Electronic) Linking ISSN: 01663542 NLM ISO Abbreviation: Antiviral Res Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: [Amsterdam ; New York : Elsevier/North-Holland Biomedical Press, c1981-
    • Subject Terms:
      SARS-CoV-2*/genetics ; SARS-CoV-2*/drug effects ; RNA, Small Interfering*/genetics ; Antiviral Agents*/pharmacology ; COVID-19*/virology; Humans ; Chlorocebus aethiops ; 5' Untranslated Regions/genetics ; Vero Cells ; Animals ; RNA, Viral/genetics
    • Abstract:
      Treatment options for COVID-19 remain limited. Here, we report the optimization of an siRNA targeting the highly conserved leader region of SARS-CoV-2. The siRNA was rendered nuclease resistant by the introduction of modified nucleotides without loss of activity. Importantly, the siRNA also retained its inhibitory activity against the emerged omicron sublineage variant BA.2, which occurred after the siRNA was designed and is resistant to other antiviral agents such as antibodies. In addition, we show that a second highly active siRNA designed against the viral 5'-UTR can be applied as a rescue molecule, to minimize the spread of escape mutations. We therefore consider our siRNA-based molecules to be promising broadly active candidates for the treatment of current and future SARS-CoV-2 variants.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: COVID-19; Chemical modifications; Leader sequence; RNAi therapy; SARS-CoV-2; siRNA
    • Subject Terms:
      SARS-CoV-2 variants
    • Publication Date:
      Date Created: 20240410 Date Completed: 20240518 Latest Revision: 20240518
    • Publication Date:
      20240519
    • Accession Number:
      10.1016/j.antiviral.2024.105879
    • Accession Number:
      38599550