Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins
Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins
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DOI：
10.1007/978-3-319-75474-1_4
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发表时间：
2018-02-16
期刊：
影响因子：
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通讯作者：
Pöhlmann S
中科院分区：
文献类型：
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作者：
Hoffmann M;Hofmann-Winkler H;Pöhlmann S
冠状病毒是一种包膜RNA病毒，可以感染哺乳动物和鸟类。人类感染全球流行的人类冠状病毒与普通感冒有关。相比之下，动物冠状病毒传播给人类可导致严重疾病：严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）分别在亚洲和中东造成数百人死亡，两者都是由Betacoronavirus属成员、SARS- cov和MERS- cov引起的，它们都是人畜共患的，从动物宿主传播给人类。目前，既没有疫苗，也没有特定的治疗方法来对抗冠状病毒在人类中的感染，迫切需要新的抗病毒策略。病毒刺突蛋白(S)介导冠状病毒感染的第一个重要步骤，即病毒进入靶细胞。为此，S蛋白严重依赖于宿主细胞蛋白酶的启动，而负责的酶是抗病毒干预的潜在靶点。最近的研究表明，内体半胱氨酸蛋白酶组织蛋白酶L和丝氨酸蛋白酶furin和TMPRSS2可以引物SARS-CoV和MERS-CoV的S蛋白，并提供证据表明，S蛋白需要在两个位点连续切割才能引物。此外，控制蛋白酶选择的机制被揭示，并获得了哪些酶促进病毒在宿主中的传播的见解。在这里，我们将提供S蛋白功能和蛋白水解引物的基本信息，然后讨论我们对SARS-CoV和MERS-CoV S蛋白引物的最新了解进展。
Coronaviruses are enveloped RNA viruses that infect mammals and birds. Infection of humans with globally circulating human coronaviruses is associated with the common cold. In contrast, transmission of animal coronaviruses to humans can result in severe disease: The severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) are responsible for hundreds of deaths in Asia and the Middle East, respectively, and are both caused by members of the genus Betacoronavirus, SARS-CoV, and MERS-CoV that were zoonotically transmitted from an animal host to humans. At present, neither vaccines nor specific treatment is available to combat coronavirus infection in humans, and novel antiviral strategies are urgently sought. The viral spike protein (S) mediates the first essential step in coronavirus infection, viral entry into target cells. For this, the S protein critically depends on priming by host cell proteases, and the responsible enzymes are potential targets for antiviral intervention. Recent studies revealed that the endosomal cysteine protease cathepsin L and the serine proteases furin and TMPRSS2 prime the S proteins of SARS-CoV and MERS-CoV and provided evidence that successive S protein cleavage at two sites is required for S protein priming. Moreover, mechanisms that control protease choice were unraveled, and insights were obtained into which enzyme promotes viral spread in the host. Here, we will provide basic information on S protein function and proteolytic priming, and we will then discuss recent progress in our understanding of the priming of the S proteins of SARS-CoV and MERS-CoV.