Abstract

Currently, the novel coronavirus pneumonia has been widespread globally, and there is no specific medicine. In response to the emergency, we employed bioinformatics methods to investigate the virus's pathogenic mechanism, finding possible control methods. We speculated in previous studies that E protein was associated with viral infectivity. The present study adopted the domain search techniques to analyse the E protein. According to the results, the E protein could bind iron or haem. The iron and haem bound by the E protein came from the attacked haemoglobin and phagocytes. When E protein was attached to haem, it synthesised oxygen and water into superoxide anions, hydrogen peroxide and hydroxyl radicals. When the iron-bound E protein and the haem-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 were exposed to infected cells, viruses that had not shed from the infected cells’ surface damaged them through “ROS attack”. In addition, 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", generating a decrease in lymphocytes. When memory B cells were exposed to the virus’s surface antigen, they were also damaged by “ROS attack”, resulting in the patient's re-infection. The virus applied the “ROS escape” to decompose hydrogen peroxide released by phagocytes into oxygen and water. The surrounding cells were replenished with oxygen, and the patient was in 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 was in the lysosome, the E protein generated ROS to damage nearby hydrolases. In this way, the virus parasitized the lysosome. Excessive hydroxyl free radicals destroyed the membrane structure of the lysosome, causing the hydrolase release from lysosome, autophagy of phagocytic cells and subsequent cell death. As a result, the colonizing phagocytes of the virus was associated with asymptomatic infection or retest-positive. Briefly, the virus inhibited the immune system through “ROS escape”, and damaged the immune system by “ROS attack”. The destruction instigated a strong cytokine storm, leading to organ failure and complications.

 抽象的

目前，新冠肺炎疫情在全球大流行，尚无特效药物。针对这一紧急情况，我们利用生物信息学方法研究病毒的致病机制，寻找可能的防治方法。我们在之前的研究中推测E蛋白与病毒感染性有关。本研究采用域搜索技术来分析E蛋白。结果表明，E蛋白可以结合铁或血红素。 E蛋白结合的铁和血红素来自被攻击的血红蛋白和吞噬细胞。当E蛋白与血红素结合时，它将氧和水合成为超氧阴离子、过氧化氢和羟​​基自由基。当铁结合的E蛋白和血红素结合的E蛋白共同作用时，它们将超氧阴离子和过氧化氢转化为氧气和水。这就是病毒的“ROS攻击”和“ROS逃逸”。 “ROS攻击”破坏病毒表面暴露的组织或细胞，“ROS逃逸”则分解攻击病毒的超氧阴离子和过氧化氢。当 NK 细胞暴露于受感染细胞时，尚未从受感染细胞表面脱落的病毒通过“ROS 攻击”对其进行破坏。此外，T细胞、B细胞等可接近病毒表面抗原的淋巴细胞也容易受到“ROS攻击”的损伤或杀死，产生淋巴细胞减少。当记忆B细胞接触到病毒的表面抗原时，它们也受到“ROS攻击”的破坏，导致患者再次感染。病毒利用“ROS逃逸”将吞噬细胞释放的过氧化氢分解为氧气和水。 周围细胞得到了氧气的补充，患者处于“快乐缺氧”状态。当吞噬细胞吞噬病毒时，E蛋白将超氧阴离子转化为氧气和水。这样，病毒就寄生在吞噬细胞的囊泡中。当病毒在溶酶体中时，E蛋白会产生ROS来损害附近的水解酶。这样，病毒就寄生在溶酶体中。过量的羟基自由基破坏了溶酶体的膜结构，导致溶酶体释放水解酶，吞噬细胞自噬，随后细胞死亡。结果，病毒的定植吞噬细胞与无症状感染或复检阳性有关。简而言之，病毒通过“ROS逃逸”抑制免疫系统，通过“ROS攻击”损害免疫系统。这种破坏引发了强烈的细胞因子风暴，导致器官衰竭和并发症。