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At present, the most researched substances with good inhibitory effects on vaccinia virus infection are mainly various nucleoside compounds and nucleoside analogs, including: inosine monophosphate (IMP) dehydrogenase inhibitors (such as Li Bavirin), S-adenosylcysteine (SAH) hydrolase inhibitors (such as adenosine analog A), orotidine monophosphate (OMP) decarboxylase inhibitors (such as pyrazolin) , cytidine triphosphate (CTP) synthase inhibitors (such as cyclopentenylcytosine (Ce-Cyd)), acyclic nucleoside carbon phosphate compounds, such as cidofovir (cidofovir), but due to such anti Poxvirus compounds have low bioavailability, high toxicity and side effects, etc., which seriously limit their comprehensive promotion and application.
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Embodiment 1
[0040] Example 1, preparation and component identification of bioactive preparation CH2009
[0041] 1. Preparation of biologically active preparation CH2009
[0042] 1. Take out the stimulating antigen (vaccinia virus) from the ultra-low temperature refrigerator at -80°C, place it in a water bath at 37°C and dissolve it quickly, add an appropriate amount of PBS, and prepare a titer of 1×10 6 TCID 50 / ml of virus fluid for inoculation.
[0043] 2. Pick healthy and mature New Zealand white rabbits, weighing about 2.7-3.0 kg, cut off the back hair, and wipe and disinfect the depilated parts with 75% alcohol cotton balls, inoculate the above virus liquid 0.05ml / inoculation point intradermally, and inoculate 100- 120 sites / rabbit.
[0044] 3. Feed 4-5 days after virus inoculation. New Zealand white rabbits with good pox symptoms, color change from ruddy to purple, skin thickening and subcutaneous edema were euthanized, and the skin was harvested within 15 minutes. The size of th...
Embodiment 2
[0059] Embodiment 2, the determination of the anti-pox virus activity of bioactive preparation CH2009
[0060] In this example, vaccinia virus and mousepox virus, which are recognized in the art as surrogate virus models of smallpox virus, will be used as the tested poxviruses to study the antiviral activity of the biologically active agent CH2009 against smallpox and other poxviruses from the cell and animal levels, respectively. .
[0061] 1. Determination of the activity of biologically active preparation CH2009 in inhibiting poxvirus infection in vitro
[0062] Tested viruses and corresponding sensitive cells: vaccinia virus WR strain (Vaccinia Virus WR Strain), ratpox virus Moscow strain (Ectromelia Viruses Moscow strain, ECTV-MOS strain), coronavirus (murine hepatitis coronavirus A59 strain, referred to as MHV- A59), type 5 adenovirus (dl309 strain), enterovirus 71 type Hn2 strain (EV71-Hn2). The sensitive cells of vaccinia virus and mousepox virus are CV-1 cells; the ...
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Abstract
The invention discloses a bioactive preparation and application of a specific anti-smallpox virus infection model strain. The application provided by the present invention is specifically the application of the bioactive preparation CH2009 in the following (1) or (2): (1) preparing a product for inhibiting poxvirus infection; (2) for inhibiting poxvirus infection; The biologically active preparation CH2009 is prepared from the inflammatory skin tissue of New Zealand white rabbits by intradermally inoculating vaccinia virus, high temperature and high pressure, solvent extraction, acid-base treatment, adsorption, elution, and centrifugal concentration. Bioactive agents specific for poxvirus infection. The present invention provides a new design strategy for the research and development of a new generation of anti-pox virus infection drugs such as smallpox, and the obtained anti-viral drugs undoubtedly have broad application prospects and huge commercial value.
Description
technical field [0001] The invention belongs to the field of antiviral drugs, and relates to a bioactive preparation and application of a specific anti-smallpox virus infection model strain. Background technique [0002] Poxviruses are a large family that can infect both humans and animals. They often cause local or systemic purulent skin lesions in infected persons, and can lead to outbreaks of infectious diseases. Of particular note is the smallpox virus, which reproduces rapidly and can be transmitted through the air at an extremely rapid rate. Patients with the virus are most contagious within 1 week of infection because their saliva contains the largest amount of smallpox virus, until After the patient's scar is peeled off, the smallpox virus can also be transmitted through the patient, which has led to many global outbreaks in human history. In the case of malignant infection, the smallpox virus causes serious diffuse damage in the tissue layer or deep layer of the sk...
Claims
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