Wenzhong Liu, Hualan Li
School of Computer Science and Engineering, Sichuan University of Science and Engineering, Zigong, China.
School of Life Science and Food Engineering, Yibin University, Yibin, China.
Autoimmunity. 2021 Jun;54(4):213-224. doi: 10.1080/08916934.2021.1913581. Epub 2021 Apr 26.
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.
目前,新型冠状病毒肺炎已在全球广泛传播,且尚无特效药物。为应对这一紧急情况,我们采用生物信息学方法研究该病毒的致病机制,寻找可能的控制方法。我们在先前的研究中推测E蛋白与病毒传染性有关。本研究采用结构域搜索技术分析E蛋白。结果显示,E蛋白可结合铁或血红素。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,它将氧气和水合成超氧阴离子、过氧化氢和羟基自由基。当结合铁的E蛋白和结合血红素的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。这些就是病毒的“ROS攻击”和“ROS逃逸”。“ROS攻击”会破坏病毒表面暴露的组织或细胞,而“ROS逃逸”则分解攻击病毒的超氧阴离子和过氧化氢。当自然杀伤细胞接触到被感染的细胞时,未从被感染细胞表面脱落的病毒会通过“ROS攻击”对其造成损害。此外,诸如T细胞和B细胞等能够接近病毒表面抗原的淋巴细胞,也容易受到“ROS攻击”的损害或杀伤,导致淋巴细胞数量减少。当记忆B细胞接触到病毒的表面抗原时,它们也会受到“ROS攻击”的损害,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。周围细胞得到氧气补充,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蛋白产生活性氧来损伤附近的水解酶。这样,病毒就寄生在溶酶体中。过量的羟基自由基破坏溶酶体的膜结构,导致水解酶从溶酶体中释放出来,吞噬细胞自噬并随后导致细胞死亡。结果,病毒在吞噬细胞中的定植与无症状感染或复测阳性有关。简而言之,病毒通过“ROS逃逸”抑制免疫系统,并通过“ROS攻击”破坏免疫系统。这种破坏引发强烈的细胞因子风暴,导致器官衰竭和并发症。