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Efficient Inhibition of SARS-CoV-2 Using Chimeric Antisense Oligonucleotides through RNase L Activation*.
Su, Xiaoxuan; Ma, Wenxiao; Feng, Di; Cheng, Boyang; Wang, Qian; Guo, Zefeng; Zhou, Demin; Tang, Xinjing.
  • Su X; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing, 100191, China.
  • Ma W; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing, 100191, China.
  • Feng D; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing, 100191, China.
  • Cheng B; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing, 100191, China.
  • Wang Q; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing, 100191, China.
  • Guo Z; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing, 100191, China.
  • Zhou D; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing, 100191, China.
  • Tang X; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing, 100191, China.
Angew Chem Int Ed Engl ; 60(40): 21662-21667, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1363645
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Oligonucleotides, Antisense / Endoribonucleases / Enzyme Activation / SARS-CoV-2 Limits: Animals / Humans Language: English Journal: Angew Chem Int Ed Engl Year: 2021 Document Type: Article Affiliation country: Anie.202105942

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Oligonucleotides, Antisense / Endoribonucleases / Enzyme Activation / SARS-CoV-2 Limits: Animals / Humans Language: English Journal: Angew Chem Int Ed Engl Year: 2021 Document Type: Article Affiliation country: Anie.202105942