Bridging the antiviral gap: A BAC-based non-infectious SARS-CoV-2 replicon reveals potent antisense gapmers.

A BAC-based non-infectious SARS-CoV-2 replicon identified the M gene as a promising antisense target with an EC50 of 6.3 nM for antiviral development.

• Why it matters: Understanding SARS-CoV-2 replication and discovering effective antivirals require safe, reliable models; current systems lack the ability to evaluate targeted RNA interventions efficiently.
• What they did: Researchers developed a non-infectious replicon based on bacterial artificial chromosome, which was transfected into HEK293T cells and used to screen antisense gapmers targeting RNA motifs within UTRs, N, and M genes, identifying five potent candidates.
• The result: The most active gapmer targeting the M gene demonstrated high potency, and four gapmers, including the lead, recognize accessible motifs in both genomic and subgenomic RNAs, suggesting dual targeting as a promising antiviral approach.