A Repurposed Drug Screen Identifies Compounds That Inhibit the Binding of the COVID-19 Spike Protein to ACE2.
A Repurposed Drug Screen Identifies Compounds That Inhibit the Binding of the COVID-19 Spike Protein to ACE2.
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DOI：
10.3389/fphar.2021.685308
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发表时间：
2021
影响因子：
5.6
通讯作者：
Smith SEP
中科院分区：
文献类型：
--
作者：
Tsegay KB;Adeyemi CM;Gniffke EP;Sather DN;Walker JK;Smith SEP
阻断 SARS-CoV-2 刺突蛋白与其受体 ACE2 之间相互作用的重新利用药物可以为新型 COVID-19 治疗或预防提供快速途径。在这里，我们从国际监管机构批准的商业药物库中筛选了 2,701 种化合物，这些化合物具有抑制重组三聚 SARS-CoV-2 刺突蛋白与重组人 ACE2 结合的能力。我们鉴定了 56 种以浓度依赖性方式抑制结合的化合物，测量了结合抑制的 IC50，并通过计算模拟了最佳抑制剂与 Spike-ACE2 结合界面的对接。最好的候选药物是硫链丝菌素、催产素、尼洛替尼和羟基喜树碱，IC50 在 4–9 μM 范围内。这些结果强调了一种有效的筛选方法，用于鉴定能够破坏 Spike-ACE2 相互作用的化合物，并鉴定几种潜在的 Spike-ACE2 相互作用抑制剂。
Repurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2,701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding in a concentration-dependent manner, measured the IC50 of binding inhibition, and computationally modeled the docking of the best inhibitors to the Spike-ACE2 binding interface. The best candidates were Thiostrepton, Oxytocin, Nilotinib, and Hydroxycamptothecin with IC50’s in the 4–9 μM range. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction, as well as identify several potential inhibitors of the Spike-ACE2 interaction.
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作者：
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通讯作者：
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