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Antisense oligonucleotide targeting COVID-19 new coronavirus, NATAC chimeric molecule and application thereof

A COVID-19, antisense oligonucleotide technology, applied in the direction of DNA / RNA fragments, recombinant DNA technology, antiviral agents, etc., can solve the problem of patients without new coronavirus

Active Publication Date: 2021-08-13
PEKING UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] At present, neutralizing antibodies or immune vaccines are mainly used to block the replication and spread of the virus, but there is no effective drug for the treatment of new coronavirus patients

Method used

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  • Antisense oligonucleotide targeting COVID-19 new coronavirus, NATAC chimeric molecule and application thereof
  • Antisense oligonucleotide targeting COVID-19 new coronavirus, NATAC chimeric molecule and application thereof
  • Antisense oligonucleotide targeting COVID-19 new coronavirus, NATAC chimeric molecule and application thereof

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experiment example 1

[0062] Experimental example 1 Design of antisense oligonucleotide and chimeric sequence and pharmacodynamic experiment of inhibiting SARS-CoV-2 virus

[0063] 1 Experimental method

[0064] 1.1 Chimeric sequence design

[0065] According to the RNA gene sequence (Gene ID: 43740570, 43740568) of the E protein and S protein of SARS-CoV-2 virus, the present invention combines the two-dimensional structural characteristics of the RNA of the E protein and the S protein, and screens out specific sites with potential As the antisense nucleic acid sequence of the targeted location, and its ability to knockout the corresponding target gene is verified. On this basis, the RNase L ligand 2′-5′adenine (A 2-5 ). Meanwhile, the corresponding nucleotide of antisense nucleic acid can be ATCG deoxynucleotide or 2'-OMe, 2'-OCH 2 CH 2 OMe or 2'-F substituted AUCG nucleotides, and the nucleic acid backbone of the entire oligonucleotide is partially or fully thioxated.

[0066] According to ...

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Abstract

The invention discloses an antisense oligonucleotide targeting a COVID-19 new coronavirus, a chimeric molecule and application thereof. Antisense nucleic acids targeting S protein and E protein are respectively designed and synthesized according to RNA (Ribonucleic Acid) sequences of spike protein and envelope protein of COVID-19 new coronavirus, and part of the antisense nucleic acids are further conjugated with a functional group 2'-5' adenine of targeting ribonuclease L to obtain the chimeric molecule. The antisense oligonucleoside nucleic acid and the antisense nucleic acid chimeric molecule (NATAC molecule) thereof provided by the invention can obviously reduce the expression level of target RNA (Ribonucleic Acid), meanwhile, obviously activate the expression of ribonuclease L, beta-interferon and interleukin 6 in cells, show obvious drug effect advantages and can effectively activate potential antiviral immunity in the cells. Therefore, the antisense oligonucleotide or the chimeric molecule provided by the invention can be used as a nucleic acid drug for preventing or treating COVID-19 new coronavirus infection.

Description

technical field [0001] The present invention relates to antisense oligonucleotides and antisense nucleic acid-based chimeric molecules of "Nucleic Acid-hydrolysis TArgeting Chimeras (NATAC)" (Nucleic Acid-hydrolysis TArgeting Chimeras, NATAC), especially related to targeting COVID- 19 new coronavirus antisense oligonucleotides and NATAC chimeric molecules prepared therefrom, the present invention further relates to their use in the preparation of drugs for the prevention or treatment of COVID-19 new coronavirus, belonging to the prevention or treatment of COVID-19 new coronavirus field. Background technique [0002] The current novel coronavirus pneumonia pandemic urgently needs effective treatment strategies. As its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has receptor recognition, membrane fusion and virus assembly links in its life process. There is a possibility of human intervention. [0003] At present, neutralizing antibodies or immune ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113C12N15/11A61K31/7088A61P31/14
CPCC12N15/1131C12N15/11A61K31/7088A61P31/14C12N2310/14C12N2320/30
Inventor 汤新景苏晓璇
Owner PEKING UNIV
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