Unknown

Dataset Information

0

Efficient Inhibition of SARS-CoV-2 Using Chimeric Antisense Oligonucleotides through RNase L Activation*.


ABSTRACT: There is an urgent need to develop antiviral drugs and alleviate the current COVID-19 pandemic. Herein we report the design and construction of chimeric oligonucleotides comprising a 2'-OMe-modified antisense oligonucleotide and a 5'-phosphorylated 2'-5' poly(A)4 (4A2-5 ) to degrade envelope and spike RNAs of SARS-CoV-2. The oligonucleotide was used for searching and recognizing target viral RNA sequence, and the conjugated 4A2-5 was used for guided RNase L activation to sequence-specifically degrade viral RNAs. Since RNase L can potently cleave single-stranded RNA during innate antiviral response, degradation efficiencies with these chimeras were twice as much as those with only antisense oligonucleotides for both SARS-CoV-2 RNA targets. In pseudovirus infection models, chimera-S4 achieved potent and broad-spectrum inhibition of SARS-CoV-2 and its N501Y and/or ΔH69/ΔV70 mutants, indicating a promising antiviral agent based on the nucleic acid-hydrolysis targeting chimera (NATAC) strategy.

SUBMITTER: Su X 

PROVIDER: S-EPMC8426974 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC9897518 | biostudies-literature
| S-EPMC8404888 | biostudies-literature
| S-EPMC10573891 | biostudies-literature
| S-EPMC6009603 | biostudies-literature
| S-EPMC6157346 | biostudies-literature
| S-EPMC7586458 | biostudies-literature
| S-EPMC9644129 | biostudies-literature
| S-EPMC6770983 | biostudies-literature
2019-10-01 | GSE133374 | GEO
| S-EPMC8643703 | biostudies-literature