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Application of gold complex in preparation of medicine for treating novel coronavirus pneumonia

A gold complex and drug technology, which can be used in drug combination, drug delivery, antiviral agents, etc., can solve the problems of ineffective inhibition of SARS-COV-2 replication and ineffective treatment of pulmonary inflammation.

Pending Publication Date: 2022-07-29
北京北工大科技园有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Many traditional medicines have been used to treat COVID-19. For example, remdesivir can effectively inhibit the replication of SARS-COV-2, but it cannot effectively treat the lung inflammation caused by infection in patients
Ruxolitinib and acatinib can directly inhibit inflammatory cytokines, but cannot effectively inhibit SARS-COV-2 replication
At present, there is a lack of a drug that can directly inhibit the replication of SARS-COV-2 and at the same time directly inhibit the inflammatory injury of the lungs of the body

Method used

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  • Application of gold complex in preparation of medicine for treating novel coronavirus pneumonia
  • Application of gold complex in preparation of medicine for treating novel coronavirus pneumonia
  • Application of gold complex in preparation of medicine for treating novel coronavirus pneumonia

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] The purified Mpro protein molecules were crystallized at 20-22 °C to form small crystal particles. These Mpro crystal particles were added with auranofin (AF) molecules or gold nanocluster (GA) molecules, respectively, at 20-22 °C. Incubate for 48h. These gold complexes release monovalent gold ions in solution to bind to protein molecules in Mpro crystals. The crystallographic synchrotron radiation combined with monovalent gold ions is subjected to crystal diffraction.

[0044] Three crystal states of SARS-COV-2 Mpro were determined: Mpro incubated with GA, Mpro incubated with AF, and Mpro incubated without gold complexes. For measurement results, see Figure 1 to Figure 3 .

[0045] The assay results showed that the molecular structures of Mpro incubated with AF and GA presented a highly similar structure, which was consistent with the reported crystal structure of Mpro. For details, see ([Z.Jin, X.Du, Y.Xu, et al. from SARS-CoV-2 and discovery of its inhibitors, N...

Embodiment 2

[0051] Detect the IC50 of AF and GA to inhibit the activity of Mpro. For specific detection methods, see (【V.Grum-Tokars,K.Ratia,A.Begaye,S.C.Baker,A.D.Mesecar,Evaluating the 3C-like proteaseactivity of SARS-Coronavirus:Recommendations for standardized assays for drug discovery, Virus Research 133, 63–73 (2008).], the activity of Mpro was determined by fluorescence energy resonance brain transfer method, and artificially synthesized fluorescently labeled peptides ((EDNAS- Glu)-Ser-Ala-Thr-Leu-Gln-Ser-Gly-Leu-Ala-(Lys-DABCYL)-Ser) as a substrate for viral protein digestion.

[0052] The measurement results are as follows:

[0053] like Image 6 As shown, the IC50 of AF is approximately equal to 0.46 μM, and the IC50 of the existing drug Ebselen is 0.67 μM (see [Z. Jin, X. Du, Y. Xu, et al. H. Yang, Structure of Mpro from SARS-CoV]. -2 and discovery of its inhibitors, Nature 582, 289–293 (2020)]), the IC50 value of AF is lower than that of Ebselen, which shows that AF can effe...

Embodiment 3

[0057] EC50, an indicator for detecting the ability of AF and GA to inhibit the replication of SARS-COV-2 virus on Vero cell model, see ([Z.Jin, X.Du, Y.Xu, Y.Deng, M.Liu, Y. Zhao,B.Zhang,X.Li,L.Zhang,C.Peng,Y.Duan,J.Yu,L.Wang,K.Yang,F.Liu,R.Jiang,X.Yang,T.You, X.Liu,X.Yang,F.Bai,H.Liu,X.Liu,L.W.Guddat,W.Xu,G.Xiao,C.Qin,Z.Shi,H.Jiang,Z.Rao,H.Yang , Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors, Nature 582, 289–293 (2020)]).

[0058] The measurement results are as follows:

[0059] like Figure 8 shown, the EC50 of AF is close to 0.83 μM, as Figure 9 As shown, the EC50 of GA is close to 7.32 μM. Both gold complexes can well inhibit virus replication in mammalian cells.

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Abstract

The invention provides application of a gold complex in preparation of a medicine for treating novel coronavirus pneumonia, and belongs to the technical field of biological medicine. The gold complex can effectively inhibit the catalytic activity of the Mpro protein and inhibit the replication of the SARS-CoV-2 live virus in the cells in the living cells. The gold complex can significantly inhibit activation of NFkB inflammatory molecular pathways of macrophages and lung bronchial cells, thereby reducing expression and secretion of inflammatory factors IL-6, IL-1beta and TNF-alpha. The gold complex can inhibit lung tissue virus replication and inhibit inflammatory injury of animal lung tissues on a COVID-19 model animal. The gold complex not only can inhibit the replication of the SARS-CoV-2 in cells and animals, but also can directly inhibit the damage of immune inflammation storm caused by virus infection to living lung tissues.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of gold complexes in the preparation of medicines for treating novel coronavirus pneumonia. Background technique [0002] Corona Virus Disease 2019 (COVID-19), referred to as "New Coronary Pneumonia". The main manifestations of COVID-19 are fever, dry cough, and fatigue. A small number of patients are accompanied by upper respiratory and gastrointestinal symptoms such as nasal congestion, runny nose, and diarrhea. Severe cases mostly develop dyspnea after 1 week, and severe cases rapidly progress to acute respiratory distress syndrome, septic shock, metabolic acidosis that is difficult to correct, coagulation dysfunction, and multiple organ failure. There is currently no drug proven to be effective in treating COVID-19. [0003] Current drug design focuses on small-molecule compounds that inhibit viral replication and antibodies / small-molecule co...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/242A61K38/06A61K38/38A61K31/7135A61K9/00A61K9/12A61P31/14A61P11/00
CPCA61K33/242A61K38/06A61K38/385A61K31/7135A61K9/0019A61K9/12A61K9/007A61K9/0014A61P31/14A61P11/00A61K2300/00A61K9/00A61K38/38A61P31/12A61K38/00A61P31/00
Inventor 高学云
Owner 北京北工大科技园有限公司
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