Following the recent outbreak of the new coronavirus pandemic (Covid-19), the rapid determination of the structure of the homo-trimeric spike glycoprotein has prompted the study reported here. The aims were to identify potential “druggable” binding pockets in the protein and, if located, to virtual screen pharmaceutical agents currently in use for predicted affinity to these pockets which might be useful to restrict, reduce, or inhibit the infectivity of the virion. Our analyses of this structure have revealed a key potentially druggable pocket where it might be viable to bind pharmaceutical agents to inhibit its ability to infect human cells. This pocket is found at the inter-chain interface that exists between two domains prior to the virion binding to human Angiotensin Converting Enzyme 2 (ACE2) protein. One of these domains is the highly mobile receptor binding domain, which must move into position to interact with ACE2, which is an essential feature for viral entry to the host cell. Virtual screening with a library of purchasable drug molecules has identified pharmaceuticals currently in use as prescription and over the counter medications that, in silico, readily bind into this pocket. This study highlights possible drugs already in use as pharmaceuticals that may act as agents to interfere with the movements of the domains within this protein essential for the infectivity processes and hence might slow, or even halt, the infection of host cells by this new coronavirus. As these are existing pharmaceuticals already approved for use in humans, this knowledge could accelerate their roll-out, through repurposing, for affected individuals and help guide the efforts of other researchers in finding effective treatments for the disease.

中文翻译：

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刺突蛋白中可药用结合口袋的鉴定揭示了潜在能够抵抗Covid-19传染性的现有药物的关键位点。

在最近新的冠状病毒大流行（Covid-19）爆发之后，快速确定同型三聚体刺突糖蛋白的结构已促使本研究报告。目的是确定蛋白质中潜在的“可吸收的”结合口袋，如果找到的话，还可以识别当前用于对这些口袋的预测亲和力的虚拟筛选药剂，这可能对限制，减少或抑制病毒体的感染性有用。我们对该结构的分析揭示了一个关键的潜在可药物化口袋，在该口袋中可以与药物结合以抑制其感染人类细胞的能力。在病毒体结合人血管紧张素转化酶2（ACE2）蛋白质之前，在两个域之间存在的链间界面处发现了这个口袋。这些结构域之一是高度可移动的受体结合结构域，该结构域必须移入位置才能与ACE2相互作用，这是病毒进入宿主细胞的基本特征。使用可购买药物分子库进行的虚拟筛选已确定了当前用作处方药的非处方药物，这些药物在计算机上很容易结合到该口袋中。这项研究强调了可能已被用作药物的药物，这些药物可能会作为干扰该蛋白在感染过程中必不可少的结构域运动的药物，因此可能减缓或什至阻止这种新型冠状病毒感染宿主细胞。由于这些是已经获准用于人类的现有药物，因此这些知识可以通过重新定位用途，