SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19.
SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19.
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DOI：
10.1042/bsr20210611
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发表时间：
2021-08-27
影响因子：
4
通讯作者：
Pretorius E
中科院分区：
文献类型：
--
作者：
Grobbelaar LM;Venter C;Vlok M;Ngoepe M;Laubscher GJ;Lourens PJ;Steenkamp J;Kell DB;Pretorius E
严重急性呼吸综合征冠状病毒2型（SARS-Cov-2）诱导的感染是2019年冠状病毒病（COVID-19）的原因，其特征是前所未有的临床病理学。最重要的病理之一是患者肺部的高凝状态和微凝块。在这里，我们研究了分离的SARS-CoV-2刺突蛋白S1亚基作为潜在的独特炎症原的作用。使用扫描电子显微镜和荧光显微镜以及质谱分析，我们研究了这种炎症因子与血小板和纤维蛋白（原）直接相互作用导致血液高凝的可能性。使用贫血小板血浆（PPP），我们表明，刺突蛋白可能会干扰血流。质谱分析还表明，当将刺突蛋白S1添加到健康PPP中时，它导致β和γ纤维蛋白（原）、补体3和凝血酶原的结构变化。在刺突蛋白S1的存在下，这些蛋白质基本上对胰蛋白酶消化具有抗性。在这里，我们认为，在某种程度上，循环中刺突蛋白的存在可能有助于COVID-19阳性患者的高凝状态，并可能导致纤维蛋白溶解的实质性损害。这种溶解性损害可能导致我们在这里和之前在COVID-19患者的血浆样本中注意到的持续性大微凝块。这一观察结果可能对COVID-19患者高凝状态的治疗具有重要的临床意义。
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies, is hypercoagulation and microclots in the lungs of patients. Here we study the effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron and fluorescence microscopy as well as mass spectrometry, we investigate the potential of this inflammagen to interact with platelets and fibrin(ogen) directly to cause blood hypercoagulation. Using platelet-poor plasma (PPP), we show that spike protein may interfere with blood flow. Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to β and γ fibrin(ogen), complement 3, and prothrombin. These proteins were substantially resistant to trypsinization, in the presence of spike protein S1. Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis. Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients. This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.