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Application of boceprevir in treating or improving novel coronavirus pneumonia

A technology of boceprevir and coronavirus, applied in the field of biomedicine, can solve the problem of insufficient antiviral activity, and achieve the effect of reducing side effects

Pending Publication Date: 2021-07-23
INST OF MICROBIOLOGY - CHINESE ACAD OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the WHO said that remdesivir had little effect on improving the mortality rate of hospitalized patients with new coronary pneumonia, and its antiviral activity was not good enough when administered alone

Method used

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  • Application of boceprevir in treating or improving novel coronavirus pneumonia
  • Application of boceprevir in treating or improving novel coronavirus pneumonia
  • Application of boceprevir in treating or improving novel coronavirus pneumonia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1. Inhibitory effect of bosaiprevir on the main protease activity of novel coronavirus

[0033] figure 1 The crystal structure of the complex of boceprevir and the main protease of the new coronavirus is shown, indicating that boceprevir can prevent the activity of the main protease of the new coronavirus. The inventors further conducted the following experiments to verify the inhibitory effect of boceprevir on the main protease activity of the novel coronavirus.

[0034] 1. Experimental method

[0035] 20 mM boceprevir solution (purchased from Taosu Biochemical) was diluted with PBS solution to obtain boceprevir solutions with concentrations of 2000 μM, 400 μM, 80 μM, 16 μM, 3.2 μM, 0.64 μM, and 0.128 μM, respectively.

[0036] Add 10 μL of the above diluted Boceprevir solutions at different concentrations to the black 96-well plate, repeat 3 wells for each concentration, and then add 30 μL of 3 μM novel coronavirus main protease solution (purchased from Suzhou...

Embodiment 2

[0039] Example 2 Inhibitory effect of boceprevir and remdesivir on viruses at the cellular level

[0040] 1. Experimental method

[0041] 20 mM boceprevir was serially diluted with DMEM medium to obtain solutions with concentrations of 200 μM, 40 μM, 8 μM, 1.6 μM, 0.32 μM, 0.064 μM, 0.0128 μM, and 0.00256 μM, respectively. At the same time, 10 mM remdesivir solution (Taosu Biochemical) was diluted with DMEM medium to 100 μM, 20 μM, 4 μM, 0.8 μM, 0.16 μM, 0.032 μM solutions as positive controls. Dilute 100% DMSO into 1% DMSO medium solution with DMEM medium as blank control.

[0042] Dilute SARS-Cov-2 virus (from the Chinese Center for Disease Control and Prevention) to 0.01 MOI with DMEM in a biosafety cabinet. Take the 96-well plate full of Vero cells (purchased from Shanghai Cell Institute) to a biological safety cabinet. Add 100 μL of 0.01 MOI virus solution to each well of the 96-well plate, and add 100 μL of DMEM (as the uninfected group) to 3 wells at the same time, a...

Embodiment 3

[0046] Example 3 Boceprevir and Remdesivir combined anti-new coronavirus experiment

[0047] The Vero cells were plated on a 24-well plate (50000 cells / well), and after 24 hours, 100 PFU of virus was used to incubate and infect for 2 hours. After infection, the monolayer cells were treated with 40 μM boceprevir, 8 μM boceprevir, 5 μM remdesivir, 1 μM remdesivir, 8 μM boceprevir + 1 μM remdesivir combination and no drug AVIcell medium was fixed (4 replicates per group). Place the plates at 37°C for 72 hours, fix with 4% paraformaldehyde, stain with 1% crystal violet, and take pictures (see Figure 7 ). From the experimental results, it can be seen that the combination of 8 μM boceprevir + 1 μM remdesivir can significantly inhibit (or basically completely inhibit) the proliferation of the new coronavirus.

[0048] According to the operation method of Example 3, the combination of 8 μM boceprevir + 100 μM remdesivir, the combination of 8 μM boceprevir + 20 μM remdesivir and th...

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Abstract

The invention relates to application of boceprevir and remdesivir in preparation of a medicine or a kit for inhibiting novel coronavirus. Experiments find that boceprevir and remdesivir are combined to efficiently inhibit proliferation of the novel coronavirus, and boceprevir and remdesivir have a good effect on treatment of novel coronavirus pneumonia.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to the application of Boceprevir and Remdesivir, a hepatitis C drug, in the preparation of drugs for treating or improving novel coronavirus pneumonia. Background technique [0002] The novel coronavirus pneumonia "COVID-19" is an acute infectious disease caused by the novel coronavirus SARS-CoV-2. Currently, there are no effective drugs or vaccines against this virus. Therefore, it is of great significance to find marketed drugs that have an inhibitory effect on the new coronavirus. [0003] The new coronavirus gene will produce two overlapping transcription and translation products in the host cell, polyprotein 1a and 1ab. After the polyprotein is hydrolyzed by the main protease and papain-like protease, a series of protein monomers with biological functions can be produced, thereby completing the replication and packaging of the virus. Antiviral drugs targeting proteases hav...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/403A61K45/06A61P31/14A61P11/00
CPCA61K31/403A61K45/06A61P31/14A61P11/00
Inventor 高福齐建勋谭文杰傅立峰叶飞李学兵冯永
Owner INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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