Confluence News reporter Chen Junkai/Taipei report
More than two years after the outbreak of the new crown pneumonia, the Taiwanese research team is still actively cracking down on how to reduce the rapid infection of the virus. The National Institutes of Health released the latest research results today (10th). The research team not only found a new mechanism for the rapid infection of cells by the new coronavirus from clinical samples, but also found “old drugs” that can be used for new purposes. Animal experiments have proved that it can reduce the scope of virus infection. , Suppress the inflammatory response and help the infected patients recover.
The team of Distinguished Researcher Tan Zehua and Assistant Researcher Zhuang Huaijia of the Center for Immunology of the National Institutes of Health found that the expression of the protein kinase MAP4K3 (also known as GLK) in cells infected with the new coronavirus was higher than that in normal cells, and the proportion of epithelial cells with high GLK expression was similar to that of normal cells. The severity of the disease is positively correlated, and in cooperation with Zhou Yanhong, a researcher at the Institute of Infectious Diseases and Vaccines of the National Institutes of Health, the use of live new coronavirus mouse experiments confirmed that this infection mechanism is the key to the large-scale infection of the new coronavirus.
Zhuang Huaijia pointed out that after the new coronavirus pneumonia virus enters the human body, it mainly infects cells by binding the spike protein on the surface of the virus to the ACE2 receptor on the surface of human respiratory epithelial cells. However, normal epithelial cells actually only express a low amount of ACE2 protein, but after infection Rapidly induced acute and severe respiratory symptoms, everything turned out to be caused by GLK causing rapid spread.
When analyzing the single-cell RNA sequencing results of COVID-19 patient samples, the research team unexpectedly found that after the new coronavirus enters host epithelial cells, the spike protein induces high expression of the protein kinase GLK, and the excessive expression of GLK will phosphorylate ACE2 Protein, ACE2 escapes the ubiquitination degradation mechanism of ubiquitinase UBR4, resulting in a stable increase of ACE2 protein on the cell surface.
Zhuang Huaijia said that, on the other hand, overexpression of GLK induces the release of exosomes loaded with ACE2 protein. If the delivery package is the same, other cells that do not express high levels of ACE2 will receive ACE2 protein after receiving cells. more likely to be infected by the new coronavirus.
It took 2 years to decipher this mechanism. Zhuang Huaijia pointed out that the research team further found old drugs that can be used new. It has been confirmed by the mouse model that the amount of ACE2 protein on the cell surface can be reduced by using a small molecule inhibitor of GLK (verteporfin). And reduce the production of ACE2 exosomes, thereby successfully inhibiting the infection rate of new coronary pneumonia virus.
Zhuang Huaijia emphasized that the effect of animal experiments is obvious, which can effectively reduce the scope of virus infection and inhibit the inflammatory response. Theoretically, the clinical application is quite good, and because it is a new use of an old drug, as long as a clinician applies to the Food and Drug Administration for additional indications, it can be Validated on the human body.
Photo Credit: Schematic Photo / Retrieved from Pexels
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