Antisense oligonucleotides targeting the SARS-CoV-2 nucleocapsid gene decrease viral titers in hamsters.

ABSTRACT: SARS-CoV-2 is a positive, single-stranded RNA coronavirus responsible for the COVID-19 pandemic. The emergence of new variants and the limited efficacy of current antivirals demonstrate the need for novel therapeutic strategies. Here, we present the design, screening, and evaluation of antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 genomic and sub-genomic RNA. By employing a combination of luminescence-based reporter assays and quantitative reverse-transcription PCR (RT-qPCR) in human cells, we selected ASO-N1, directed against the nucleocapsid RNA, as the best candidate to be validated in vivo. Hamsters infected with SARS-CoV-2 were treated with an initial intranasal ASO dose, followed by daily systemic administration. ASO-treated animals showed significantly improved c

SUBMITTER: Fitzpatrick C 

PROVIDER: S-EPMC12275150 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature