Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an emerging new viral pathogen that causes severe respiratory disease. SARS-CoV-2 is responsible for the outbreak of COVID-19 pandemic worldwide. As there are no confirmed antiviral drugs or vaccines currently available for the treatment of COVID-19, discovering potent inhibitors or vaccines are urgently required for the benefit of humanity. The glycosylated Spike protein (S-protein) directly interacts with human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of S-protein. As the S-protein is exposed to the surface and is essential for entry into the host, the S-protein can be considered as a first-line therapeutic target for antiviral therapy and vaccine development. In silico screening, docking, and molecular dynamics simulation studies were performed to identify repurposing drugs using DrugBank and PubChem library against the RBD of S-protein. The study identified a laxative drug, Bisoxatin (DB09219), which is used for the treatment of constipation and preparation of the colon for surgical procedures. It binds nicely at the S-protein–ACE2 interface by making substantial π-π interactions with Tyr505 in the ‘Site 1’ hook region of RBD and hydrophilic interactions with Glu406, Ser494, and Thr500. Bisoxatin consistently binds to the protein throughout the 100 ns simulation. Taken together, we propose that the discovered molecule, Bisoxatin may be a promising repurposable drug molecule to develop new chemical libraries for inhibiting SARS-CoV-2 entry into the host.

中文翻译：

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通过计算方法鉴定作为人冠状病毒 SARS-CoV-2 Spike 蛋白抑制剂的再利用药物

严重急性呼吸系统综合症冠状病毒 (SARS-CoV-2) 是一种新兴的病毒病原体，可引起严重的呼吸道疾病。SARS-CoV-2 是造成全球 COVID-19 大流行的罪魁祸首。由于目前没有确认的抗病毒药物或疫苗可用于治疗 COVID-19，因此迫切需要发现有效的抑制剂或疫苗以造福人类。糖基化的 Spike 蛋白（S 蛋白）通过 S 蛋白的受体结合域 (RBD) 直接与人血管紧张素转换酶 2 (ACE2) 受体相互作用。由于 S 蛋白暴露于表面并且是进入宿主所必需的，因此可以将 S 蛋白视为抗病毒治疗和疫苗开发的一线治疗靶点。硅片筛选、对接、并进行了分子动力学模拟研究，以使用 DrugBank 和 PubChem 库来识别针对 S 蛋白 RBD 的再利用药物。该研究确定了一种通便药物 Bisoxatin (DB09219)，用于治疗便秘和为手术准备结肠。它通过与 RBD 的“站点 1”钩区域中的 Tyr505 产生大量的 π-π 相互作用以及与 Glu406、Ser494 和 Thr500 的亲水性相互作用，在 S-蛋白-ACE2 界面上很好地结合。Bisoxatin 在整个 100 ns 模拟过程中始终与蛋白质结合。总之，我们提出发现的分子 Bisoxatin 可能是一种有前途的可重复利用的药物分子，可用于开发新的化学库以抑制 SARS-CoV-2 进入宿主。