Biological and Medicinal Chemistry

COVID-19: Captures Iron and Generates Reactive Oxygen Species to Damage the Human Immune System



At present, the novel coronavirus pneumonia has been widespread worldwide, and there is no specific medicine. In response to the emergency, we adopted bioinformatics methods to study the virus's pathogenic mechanism and found possible control methods. We speculated in previous studies that E protein was related to viral infectivity. This study adopted the domain search techniques to analyze the E protein. The results showed that the E protein could bind iron or heme. The iron and heme bound by the E protein came from the attacked hemoglobin and phagocytes. When E protein attached to heme, it synthesized oxygen and water into superoxide anions, hydrogen peroxide, and hydroxyl radicals. When the iron-bound E protein and the heme-bound E protein worked together, they converted superoxide anions and hydrogen peroxide into oxygen and water. These were the “ROS attack” and “ROS escape” of the virus. “ROS attack” damaged the tissues or cells exposed on the surface of the virus, and “ROS escape” decomposed the superoxide anion and hydrogen peroxide that attacked the virus. When NK cells exposed to infected cells, viruses that had not shed from the infected cells’ surface damaged them through “ROS attack”. Lymphocytes such as T cells and B cells, which could be close to the antigen of the virus surface, were also easily damaged or killed by the "ROS attack", resulting in a decrease in lymphocytes. When memory B cells exposed to the virus’s surface antigen, “ROS attack” also damaged them, resulting in the patient's re-infection. The virus used the “ROS escape” to decompose hydrogen peroxide released by phagocytes into oxygen and water. The surrounding cells were replenished with oxygen, and the patient had a “happy hypoxia” state. When the phagocytes swallowed the virus, the E protein converted superoxide anions into oxygen and water. In this way, the virus parasitized in the vesicles of the phagocyte. While virus in the lysosome, the E protein generated ROS to damage nearby hydrolases. The virus parasitized the lysosome in this way. Excessive hydroxyl free radicals destroyed the membrane structure of the lysosome, causing the lysosome to release hydrolase, phagocytic cells autophagy and died. Therefore, the colonizing phagocytes of the virus was related to asymptomatic infection or retest-positive. In short, the virus inhibited the immune system through “ROS escape”, and damaged the immune system by “ROS attack”. The destruction instigated a strong cytokine storm and led to organ failure and complications. This theory is only used for academic discussion.We hoped this discovery would help prevent severe epidemics and save more lives.


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