Polypeptide inhibitor for inhibiting ten corona viruses

A coronavirus and human coronavirus technology, applied in viral peptides, antiviral agents, viruses, etc., can solve problems such as major side effects, capping system effects, etc., and achieve the effects of inhibiting replication, high specificity and application prospects

Active Publication Date: 2017-10-13
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these non-specific inhibitory drugs are likely to affect the capping system of the ho...

Method used

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  • Polypeptide inhibitor for inhibiting ten corona viruses
  • Polypeptide inhibitor for inhibiting ten corona viruses
  • Polypeptide inhibitor for inhibiting ten corona viruses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The features and advantages of the present invention can be further understood through the following detailed description in conjunction with the accompanying drawings. The examples provided are only illustrative of the method of the present invention and do not limit the rest of the present disclosure in any way. [Example 1] Design and verification of polypeptide inhibitors

[0041] 1. Based on the crystal structure of the non-structural protein nsp10 and nsp16 complex of SARS coronavirus as a reference, the analysis and the principle of polypeptide inhibition

[0042] figure 1 Shown is a diagram of the crystal structure of the co-crystal of the nsp10 and nsp16 complex. figure 1 In A, the green one is nsp10, and the light blue one is nsp16. It can be seen that the two interact through the protein surface to form a complex. According to our previous studies, nsp10 promotes the binding of nsp16 to the substrate (viral RNA) and the binding to the substrate SAM, thereby...

Embodiment 2

[0051] [Example 2] The screening process of P21.

[0052] Reagent preparation:

[0053] 10× Reaction Buffer: 500mM Tris-HCl (pH 7.5), 50mM KCl, 10mM MgCl 2 ,10 mM DTT,400units RNase inhibitor,0.01mM SAM

[0054] isotope 3 H substrate: S-adenosyl[methyl-3H]methionine (67.3Ci / mmol, 0.5μCi / μl)

[0055] Viral RNA substrate: m7GpppA-RNA (derived from MERS coronavirus RNA)

[0056] RNA purification filler: activated DEAE-Sephadex TM A-25

[0057] Implementation steps:

[0058] 1. In a 25μl reaction system [50mM Tris-HCl (pH 7.5), 1mM MgCl 2 , 5mM KCl, 1mMDTT, 40units RNase inhibitor, 0.01mM SAM] were added to the purified MERS coronavirus nonstructural proteins nsp16 (3.3μM) and nsp10 (10μM).

[0059] 2. Add peptides P57, P41, P29, P21, P16, P8, P4 with a final concentration of 200 μM to the reaction, and other control groups and mix well.

[0060] 3. Add 0.5μCi S-adenosyl[methyl-3H]methionine (67.3 Ci / mmol, 0.5μCi / μl) to each reaction system and mix well.

[0061] 4. Add...

Embodiment 4

[0082] [Example 4] TCP21 inhibits the methyltransferase activity of ten kinds of coronavirus non-structural proteins nsp16 such as MERS (viral RNA capping system activity)

[0083] Reagent preparation:

[0084] 10× Reaction Buffer: 500mM Tris-HCl (pH 7.5), 50mM KCl, 10mM MgCl 2 ,10 mM DTT,400units RNase inhibitor,0.1mM SAM

[0085] isotope 3 H substrate: S-adenosyl[methyl-3H]methionine (67.3Ci / mmol, 0.5μCi / μl)

[0086] Viral RNA substrate: m7GpppA-RNA (derived from MERS coronavirus RNA)

[0087] RNA purification filler: activated DEAE-Sephadex TM A-25

[0088] Implementation steps:

[0089] 1. In a 25μl reaction system [50mM Tris-HCl (pH 7.5), 1mM MgCl 2 , 5mM KCl, 1mMDTT, 40units RNase inhibitor, 0.01mM SAM] were added to the purified MERS and other ten coronavirus non-structural proteins nsp16 (1.6μM) and nsp10 (9.6μM).

[0090] 2. Add 100 and 200 μM peptide inhibitor TCP21 to the reaction, and other control groups were mixed evenly. The amino acid sequence of TCP21...

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PUM

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Abstract

The invention discloses a polypeptide inhibitor for inhibiting ten corona viruses, and belongs to the technical field of biological medicines. The polypeptide inhibitor comprises 1) an amino acid sequence as shown as SEQ ID No.1 (Sequence Identifier Number 1), or 2) a sequence which is obtained by replacement, addition and/or one or more amino deletion by the amino acid sequence as shown as SEQ ID No.1, has an equivalent function and is derived by the sequence as shown as SEQ ID No.1, or 3) a core sequence of the sequence as shown as SEQ ID No.1, wherein the core sequence is SEQ ID No.2. The polypeptide inhibitor has very high broad spectrum performance, and can simultaneously inhibit ten different corona viruses, therefore, outbreak of an infective respiratory disease caused by some unknown novel corona virus in some uncertain time point in future can be rapidly and timely coped with at the first time, and the defects that the current single therapeutic drug is high in side effect and a sequela is easily resulted are overcome.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. In particular, it relates to a polypeptide inhibitor that can be used to inhibit the capping modification function and its replication, transcription and translation of ten kinds of coronaviruses such as MERS-CoV. Background technique [0002] Coronavirus (Coronavirus) is a kind of pathogenic RNA virus that infects humans, poultry, and livestock, and then causes respiratory tract, digestive tract inflammation, and diarrhea. Ten kinds of coronaviruses involved in the present invention are respectively infectious bronchitis virus (infectious bronchitis virus is called for short IBV), porcine transmissible gastroenteritis virus (transmis siblegastroenteritis virus is called for short TGEV), feline coronavirus (feline coronavirus is called for short FCoV), mouse Hepatitis virus (mouse hepatitis virus referred to as MHV), human coronavirus 229E (Human coronavirus 229E referred to as HCoV-229E), h...

Claims

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Application Information

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IPC IPC(8): C07K14/165C07K14/17C12N15/50C12N15/63A61K38/16A61P31/14
CPCA61K38/00C07K14/005C12N2770/20022
Inventor 郭德银陈宇王石雷
Owner WUHAN UNIV
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