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

Antiviral Res. 2024 Apr 8:105879. doi: 10.1016/j.antiviral.2024.105879. Online ahead of print.ABSTRACTTreatment 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.PMID:38599550 | DOI:10.1016/j.antiviral.2024.105879

Source: Antiviral Research - April 10, 2024 Category: Virology Authors: Beatrice Tolksdorf Julian Heinze Daniela Niemeyer Viola R öhrs Johanna Berg Christian Drosten Jens Kurreck Source Type: research