Scientists have found new drug targets for antiviral infection

Center for excellence and innovation of molecular cell science, Chinese Academy of Sciences (Biochemistry and cell biology Wang Hongyan's research group and Weibin (former researcher of Wuhan Virus Research Institute, Chinese Academy of Sciences) Laboratory of Shanghai University found that the intracellular 7-dehydrocholesterolereductase (DHCR7) decreased the function and mechanism of innate immune and antiviral infection of the body, and blocking its activity could significantly enhance the "guard" of human immune system macrophages to eliminate Zika virus, influenza virus and herpes The "fighting power" of viruses and other viruses This study provides a new drug target for resistance to new or highly pathogenic virus infection Relevant papers have been published in immunity online recently, and relevant inventions have applied for patents Cholesterol is closely related to cardiovascular disease, but new research shows that reducing cholesterol synthesis of macrophages can help protect against virus infection In this study, DHCR7, a reductase that can "abnormally express" DNA virus and RNA virus infection, was screened and locked It can convert 7-dehydrocholesterol (7-DHC) into cholesterol The researchers found that blocking the activity of DHCR7 can not only reduce cholesterol, but also promote the accumulation of 7-DHC, and ultimately enhance the production level of type I interferon (such as IFN β), so as to effectively prevent virus infection The researchers found that the construction of the "signal pathway" is similar to the "baton" transmission: 7-DHC, like the radar on the membrane surface of macrophages, transmits the "danger signal" of virus invasion to the protein kinase Akt3 in macrophages, promoting Akt3 activation; Akt3 then combines with IRF3, which is responsible for gene transcription, to "inform" IRF3 to generate more IFN β in an emergency This signaling pathway acts like a "rally" and eventually allows macrophages to clear the invading virus as soon as possible In the study, the researchers also found that tamoxifen, a breast cancer chemotherapy drug, has a new function of inhibiting herpes virus and Zika virus infection, which was approved by the US Food and drug administration to inhibit DHCR7 activity.