Small interfering nucleic acid for inhibiting novel coronavirus, and composition and applications thereof

A new type of nucleotide technology, applied in the field of biomedicine, can solve the problem of lack of effective antiviral drugs for SARS-CoV-2 virus

Active Publication Date: 2020-05-12
SUZHOU GENEPHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Scientists and clinicians around the world are working rapidly to combat the respiratory disease COVID-19 caused by the new coronavirus, but there is still

Method used

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  • Small interfering nucleic acid for inhibiting novel coronavirus, and composition and applications thereof
  • Small interfering nucleic acid for inhibiting novel coronavirus, and composition and applications thereof
  • Small interfering nucleic acid for inhibiting novel coronavirus, and composition and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Synthesis of small interfering nucleic acids

[0079] The novel coronavirus (SARS-CoV-2) genome (Genebank accession number MN988668.1) (SEQ ID NO: 227) with a relatively conserved sequence was selected as the template. A 21bp nucleotide sequence was selected for the conserved region of the SARS-CoV-2 gene, and a small interfering nucleic acid (siRNA) was designed.

[0080] The siRNA designed in this example was synthesized by Shanghai Gemma Pharmaceutical Technology Co., Ltd., and the sequence of the synthesized siRNA is shown in Table 1.

[0081] Table 1

[0082]

[0083]

[0084]

[0085]

[0086]

[0087] As shown in Table 1, this embodiment also sets the siRNA with the nucleotide sequence of the sense strand as shown in SEQIDNO: 207 and the nucleotide sequence of the antisense strand as shown in SEQIDNO: 208, and the number is M-mimicsNC, which is related to the new coronavirus The virus (SARS-CoV-2) gene has no irrelevant sequence corresponding to ...

Embodiment 2

[0089] Synthesis of Modified Small Interfering Nucleic Acids

[0090] After chemically modifying the sense strand and antisense strand of the sequence in Table 1, the modified siRNA shown in Table 2 is obtained, that is, the nucleosides of bases 1, 2, 3, 19, 20, and 21 of the sense strand The 2' hydroxyl group of the pentose group in the acid residue is all modified by methoxy, the phosphate group between the 1st, 2nd and 3rd bases of the sense chain is a phosphorothioate group, and the sense chain 1st The phosphate group between the 19th, 20th, and 21st bases is a phosphorothioate group; the pentose sugar group in the nucleotide residues of the 1st, 2nd, 3rd, 19th, 20th, and 21st bases in the antisense strand The 2' hydroxyl groups of the antisense strands are all modified by methoxy groups, the phosphate groups between the 1st, 2nd, and 3rd bases of the antisense chain are phosphorothioate groups, and the 19th, 20th, and 21st bases of the antisense strand The phosphate grou...

Embodiment 3

[0098] Dual luciferase reporter gene plasmid construction

[0099] The dual luciferase reporter gene plasmid used in this example is the GP-miRGLO plasmid (the sequence of the empty vector is shown in its manual), which was purchased from Promega, and its map information figure 1 shown. Insert a novel coronavirus (SARS-CoV-2) genome sequence into the GP-miRGLO plasmid to prepare the dual luciferase reporter gene plasmid shown in Table 3.

[0100] table 3

[0101]

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PUM

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Abstract

The invention discloses small interfering nucleic acid for inhibiting novel coronavirus, and a composition and applications thereof. The siRNA contains a positive-sense strand and a antisense strand;the siRNA is 21-si-SP-2069, 21-si-SP-2289, 21-si-SP-3292, 21-si-P3-242, 21-si-P8-62, 21-si-P8-164, 21-si-P10B-158, 21-si-P14-19, 21-si-NP-722, 21-si-NP-1123, 21-si-NS-2139 or 21-si-NS-2798; and partial nucleotide of the positive-sense strand or the antisense strand is 2'-O-methyl ribonucleotide, and partial phosphate groups are phosphorothioate groups. The provided brand-new siRNA and the composition thereof can effectively prevent and/or treat novel coronavirus.

Description

technical field [0001] The present invention relates to the field of biomedical technology, in particular to a small interfering nucleic acid that inhibits gene expression of a novel coronavirus and the application of the small interfering nucleic acid in the preparation of a pharmaceutical composition for preventing and / or treating novel coronavirus pneumonia. Background technique [0002] In late 2019 and early 2020, a new type of coronavirus pneumonia (CoronaVirusDisease2019, COVID-19) broke out in Wuhan, China. COVID-19 is an acute infectious pneumonia, and researchers have found that its pathogen is caused by a novel betacoronavirus not previously found in humans, which was subsequently named SARS-CoV by the World Health Organization (WHO)- 2. The initial symptoms of COVID-19 patients are mostly fever, fatigue and dry cough, and gradually develop severe symptoms such as dyspnea. The prognosis of most patients is good, and acute respiratory distress syndrome, septic sh...

Claims

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Application Information

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IPC IPC(8): C12N15/113A61K48/00A61K31/713A61P31/14A61P11/00
CPCC12N15/1131A61K31/713A61P31/14A61P11/00C12N2310/141C12N2310/315C12N2310/321
Inventor 董长贵胡荣宽张佩琢杜永华汪昕张紫楠李琴杜宏
Owner SUZHOU GENEPHARMA
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