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Scientists have discovered a new anti-cancer drug-EBV protein inhibitor

2021-07-13
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Epstein-Barr virus (EBV) is a herpes virus that is pathogenic to humans. It has been found to be associated with nasopharyngeal cancer, some gastric cancer, laryngeal cancer and Hodgkin’s lymphoma. Although the proportion of EB virus directly causing cancer is very low, because of the high proportion of human infections, the eradication of cancer caused by EB virus has been listed as a challenge by scientists. Recently, a scientist described a class of Epstein-Barr nuclear antigen 1 (EBNA1) inhibitors of the EBV protein, and studied the therapeutic effects of these inhibitors on EBV-related mouse tumor models, and found that the tumor growth of all mice Significantly slow down, and combined with radiotherapy or chemotherapy can further enhance the therapeutic effect.

The most common disease caused by EB virus infection in humans is infectious mononucleosis. Because it is mainly transmitted through saliva, it has a higher incidence among young people. It is also called “kissing disease”, but most infections All are asymptomatic. According to statistics in the United States, the EB virus infection rate of 5-year-old children has reached about 50%, and the infection rate at the age of 40 is as high as 90%. Once stimulated by genetics, living habits (dietary structure), and other carcinogenic factors, some virus carriers will relapse and even cause cancer.

Some researchers have made a mouse whose B lymphocytes can express the Epstein-Barr virus membrane protein LMP1, which can be used as a mouse tumor model of lymphoma. This mouse tumor model expressing LMP1 protein can be used for EB virus-induced immune surveillance and lymphoma research, and can verify whether the new method of treating lymphoma is effective. Medicilon provides a variety of effective animal models according to customer needs to test the effectiveness of drugs. Experimental animals include non-human primates, dogs, mice, rats, rabbits, guinea pigs, nude mice and other species. At present, a number of effective animal tumor models have been established, and they have been verified by multiple parties and tested in long-term practice.

Studies have found that the most fundamental reason for the canceration of a small number of patients infected with Epstein-Barr virus is that the immune system lacks an effective attack on Epstein-Barr virus. As a result, these viruses can reproduce unscrupulously in cells, secrete a large number of proteins and send out wrong messages, making the original The uncontrolled replication of normal cells produces cancer. EBNA1 is a viral determinant antigen that appears in the early stage of EB virus-infected cells. It plays an important role in cell transformation and maintenance, and its virus will continue to exist in the final stage of the replication cycle. It has been reported that EBNA1 is used in the detection of nasopharyngeal carcinoma. The sensitivity and specificity of (NPC) are as high as 90%, and EBNA1 is considered to be an ideal indicator for the detection of nasopharyngeal carcinoma.

The corresponding author of the study, Professor Paul M. Lieberman, head of the Gene Expression and Regulation Research Group of the Weststar Institute, said that the characteristics of EBNA1 and the special structure of this protein make it an attractive therapeutic target. Based on the 3D structure of this protein, Lieberman and colleagues created a class of small molecule inhibitors that can inhibit its binding protein, and verified it on EBV-infected NPC cells.

Researchers conducted studies on EBV-related mouse tumor models derived from transplanted tumor cells or patient-derived tumor cells, and found that these inhibitors can significantly slow down the growth of tumors in all mice, which is compared with radiotherapy or The combined use of chemotherapy can further enhance the therapeutic effect. According to Dr. Troy E. Messick, the first author of the study, co-corresponding author, and senior scientist in Lieberman’s laboratory, it took nearly a decade for this study from a concept to now find a clinical drug candidate. They are very satisfied with the efficacy of these inhibitors in a series of preclinical studies and look forward to further in-depth studies.

EBNA1 inhibitors have very important effects on the gene expression of EBV and host cells, which are related to the reduction of EBV DNA replication and the inhibition of EBV-derived tumor-promoting signals. Importantly, the experimental results show that the treatment effect is significant, and there is no sign of drug resistance after long-term use.

EBV is a human herpes virus with a complex genome and is closely related to many human diseases. The cancers caused by EBV are mainly lymphoma, laryngeal cancer, nasopharyngeal cancer and gastric cancer. Scientists aim to fundamentally solve the carcinogenic problem of EBV infection through a variety of methods such as vaccine prevention, immunological diagnosis and treatment. Scientists from the United States discovered EBNA1 inhibitors and studied them in mouse tumor models. The curative effect is remarkable. It can be said that it is a major discovery in the development of EBV drugs and has very important significance.

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