The ongoing COVID-19 pandemic has already caused over a million deaths worldwide, and this death toll will be much higher before effective treatments and vaccines are available. The causative agent of the disease, the coronavirus SARS-CoV-2, shows important similarities with the previously emerged SARS-CoV-1, but also striking differences. First, SARS-CoV-2 possesses a significantly higher transmission rate and infectivity than SARS-CoV-1 and has infected in a few months over 60 million people. Moreover, COVID-19 has a systemic character, as in addition to the lungs it also affects heart, liver, and kidneys among other organs of the patients, and causes frequent thrombotic and neurological complications. In fact, the term “viral sepsis” has been recently coined to describe the clinical observations. Here I review current structure-function information on the viral spike proteins and the membrane fusion process to provide plausible explanations for these observations. I hypothesize that several membrane-associated serine proteinases (MASPs), in synergy with or in place of TMPRSS2, contribute to activate the SARS-CoV-2 spike protein. Relative concentrations of the attachment receptor, ACE2, MASPs, their endogenous inhibitors (the Kunitz-type transmembrane inhibitors, HAI-1/SPINT1 and HAI-2/SPINT2, as well as major circulating serpins) would determine the infection rate of host cells. The exclusive or predominant expression of major MASPs in specific human organs suggests a direct role of these proteinases in e.g. heart infection and myocardial injury, liver dysfunction, kidney damage, as well as neurological complications. Thorough consideration of these factors could have a positive impact on the control of the current COVID-19 pandemic.

中文翻译：

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几种膜结合丝氨酸蛋白酶引发SARS-CoV-2 S蛋白可能解释病毒感染力增强和全身COVID-19感染

正在进行中的COVID-19大流行已在全球造成超过100万人死亡，在提供有效的治疗方法和疫苗之前，这种死亡人数将大大增加。该疾病的病原体冠状病毒SARS-CoV-2与以前出现的SARS-CoV-1显示出重要的相似之处，但也有显着差异。首先，SARS-CoV-2具有比SARS-CoV-1更高的传播率和传染性，并且在短短几个月内感染了超过6000万人。而且，COVID-19具有全身性，因为它除了影响肺部外，还影响患者的其他器官的心脏，肝脏和肾脏，并引起频繁的血栓形成和神经系统并发症。实际上，最近已经创造了术语“病毒性败血症”来描述临床观察。在这里，我回顾了有关病毒刺突蛋白和膜融合过程的当前结构功能信息，以为这些观察提供合理的解释。我假设与TMPRSS2协同作用或代替TMPRSS2的几种膜相关丝氨酸蛋白酶（MASP）有助于激活SARS-CoV-2刺突蛋白。附着受体，ACE2，MASPs，其内源性抑制剂（Kunitz型跨膜抑制剂，HAI-1 / SPINT1和HAI-2 / SPINT2以及主要的循环丝氨酸蛋白酶抑制剂）的相对浓度将决定宿主细胞的感染率。主要MASP在特定人体器官中的排他性表达或优势表达提示这些蛋白酶在例如心脏感染和心肌损伤，肝功能障碍，肾脏损害以及神经系统并发症中具有直接作用。