Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection.

ABSTRACT: The continuous evolution of SARS-CoV-2 variants complicates efforts to combat the ongoing pandemic, underscoring the need for a dynamic platform for the rapid development of pan-viral variant therapeutics. Oligonucleotide therapeutics are enhancing the treatment of numerous diseases with unprecedented potency, duration of effect, and safety. Through the systematic screening of hundreds of oligonucleotide sequences, we identified fully chemically stabilized siRNAs and ASOs that target regions of the SARS-CoV-2 genome conserved in all variants of concern, including delta and omicron. We successively evaluated candidates in cellular reporter assays, followed by viral inhibition in cell culture, with eventual testing of leads for in vivo antiviral activity in the lung. Previous attempts to del

SUBMITTER: Hariharan VN 

PROVIDER: S-EPMC10089225 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature