The Russian-German Academy of Medical and Biotechnological Sciences, Moscow, 121205, Skolkovo, Russia.
Ivanovsky Institute of Virology, Gamaleya Scientific Research Institute of Epidemiology and Microbiology, Moscow, 123098, Russia.
Biochemistry (Mosc). 2020 May;85(5):523-530. doi: 10.1134/S0006297920050016.
In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic classes aimed at certain viral targets: inhibitors of viral RNA polymerase, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S allowing virus entry into the target cell, inhibitors of virus uncoating in cellular endosomes, compounds of exogenous interferons, and compounds of natural and recombinant virus-neutralizing antibodies. In the second stage, when the multiplication of the virus decreases and threatening pathological processes of excessive inflammation, acute respiratory distress syndrome, pulmonary edema, hypoxia, and secondary bacterial pneumonia and sepsis events develop, a pathogenetic therapeutic approach including extracorporeal blood oxygenation, detoxification, and anti-inflammatory and anti-bacterial therapy seems to be the most effective way for the patient's recovery.
在 SARS、MERS 和 COVID-19 冠状病毒引起的呼吸道感染过程的发病机制中,可以区分两个阶段:早期(病因学)和晚期(发病机制)。在第一阶段,当病毒在宿主免疫反应不足的情况下大量繁殖和积累时,使用抑制病毒复制的化学治疗剂来抑制疾病的发展是合理的。本文考虑了针对特定病毒靶标的六大化学治疗类别:病毒 RNA 聚合酶抑制剂、病毒蛋白酶 Mpro 抑制剂、允许病毒进入靶细胞的病毒蛋白 S 蛋白水解激活抑制剂、病毒在细胞内内体脱壳抑制剂、外源性干扰素化合物和天然及重组病毒中和抗体化合物。在第二阶段,当病毒繁殖减少且威胁到过度炎症、急性呼吸窘迫综合征、肺水肿、缺氧以及继发性细菌性肺炎和败血症等病理过程时,包括体外血液氧合、解毒以及抗炎和抗菌治疗在内的发病机制治疗方法似乎是患者康复的最有效途径。