Tan Zehua, Distinguished Researcher of the Institute of Immunomedicine Research of the National Institutes of Health, and Assistant Researcher Zhuang Huaijia, cooperated with Zhou Yanhong, a researcher of the Institute of Infectious Diseases and Vaccines of the National Institutes of Health, using live new coronavirus mouse experiments to confirm the key to the large infection of the new coronavirus, and also explain the new crown vaccine Mechanisms that cause side effects.
It has been more than two years since the outbreak of the new crown pneumonia epidemic, which has spread to as many as 580 million people around the world and killed more than 6 million people. Tan Zehua, Distinguished Researcher of the Institute of Immunomedicine Research of the National Institutes of Health, and Assistant Researcher Zhuang Huaijia, cooperated with Zhou Yanhong, a researcher of the Institute of Infectious Diseases and Vaccines of the National Institutes of Health, using live new coronavirus mouse experiments to confirm the key to the large infection of the new coronavirus, and also explain the new crown vaccine Mechanisms that cause side effects. The research results will be published in the world-renowned medical journal “EMBO Molecular Medicine” in July 2022.
Excessive protein kinase GLK is the key to massive new coronavirus infection
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The research team analyzed the single-cell RNA sequencing results of COVID-19 patient samples and unexpectedly found that after the new coronavirus entered the host epithelial cells, the spike protein would induce high expression of the protein kinase GLK. Continued use of proteomics and various biochemical experiments confirmed that overexpressed GLK phosphorylates ACE2 protein, allowing ACE2 to escape the ubiquitination degradation mechanism of ubiquitinase UBR4, resulting in a stable increase of ACE2 protein on the cell surface.
The research team analyzed the single-cell RNA sequencing results of COVID-19 patient samples and unexpectedly found that after the new coronavirus entered the host epithelial cells, the spike protein would induce high expression of the protein kinase GLK. (https://www.freepik.com/)
At the same time, overexpression of GLK induces the release of exosomes loaded with ACE2 protein, which are delivered to other cells that do not express high levels of ACE2. These cells that have received ACE2 protein are more likely to be infected by the new coronavirus. The researchers analyzed the serum samples of COVID-19 patients and found that GLK phosphorylated ACE2 protein and exosomes loaded with ACE2 protein increased significantly compared with normal samples.
These research results confirm that the excess expression of protein kinase GLK is a key factor in the pathogenesis of COVID-19, and also explain the reason why the new coronavirus quickly induces clinical symptoms and is easy to spread.
Drugs that can modulate GLK and ACE2 into potential new crown inhibitor candidates
The research team used the mouse model to conduct animal experiments. When the small molecule inhibitor of GLK (verteporfin) was used to reduce the amount of ACE2 protein on the cell surface and reduce the production of ACE2 exosomes, the infection rate of the new coronary pneumonia virus in mice was successfully suppressed. . Verteporfin and other drugs that can modulate GLK and ACE2 have the potential to be candidate drugs for inhibiting new coronavirus infection.
Vaccine side effects may be related to spike protein
In addition, the research results can further explain the mechanism of severe inflammatory response caused by new coronary pneumonia and the side effects of new coronary pneumonia vaccine. The main component of the new coronary pneumonia vaccine is spike protein or spike protein RNA. Spike protein may also stimulate and induce immune cells to produce excessive GLK, resulting in a strong inflammatory response and side effects of the vaccine. It is expected that by further unraveling the pathogenic mechanism of the disease, it will help the development and screening of therapeutic drugs and vaccines, and promote the well-being of all people.
This article is reproduced with permission from[Health and Medical Network]reporter Lin Yiting The National Institutes of Health discovers the “rapid infection mechanism of the new coronavirus”, which is conducive to the development of drugs and vaccines
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