Frontispiece: Efficient Inhibition of SARS‐CoV‐2 Using Chimeric Antisense Oligonucleotides through RNase L Activation

SARS‐CoV‐2 In their Communication on page 21662, Xinjing Tang et al. report the efficient inhibition of SARS‐CoV‐2 using chimeric antisense oligonucleotides through RNase L activation.

Frontispiz: Efficient Inhibition of SARS‐CoV‐2 Using Chimeric Antisense Oligonucleotides through RNase L Activation

SARS‐Cov‐2 In der Zuschrift aus S. 21830 berichten Xinjing Tang et al. über die effiziente Hemmung von SARS‐CoV‐2 mit chimären Antisense‐Oligonukleotiden durch Aktivierung der RNase L.

Efficient Inhibition of SARS‐CoV‐2 Using Chimeric Antisense Oligonucleotides through RNase L Activation

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.

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

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.