Tsegay Kaleb B, Adeyemi Christiana M, Gniffke Edward P, Sather D Noah, Walker John K, Smith Stephen E P
bioRxiv. 2021 Apr 8:2021.04.08.439071. doi: 10.1101/2021.04.08.439071.
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 2701 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 by <90%, measured the EC of binding inhibition, and computationally modeled the docking of the best inhibitors to both Spike and ACE2. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction as well as identifying several potential inhibitors that could serve as templates for future drug discovery efforts.
能够阻断严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白与其受体血管紧张素转换酶2（ACE2）之间相互作用的重新利用药物，可能为新型冠状病毒肺炎（COVID-19）的治疗或预防提供一条快速途径。在此，我们从国际监管机构批准的商业药物库中筛选了2701种化合物，以评估它们抑制重组三聚体SARS-CoV-2刺突蛋白与重组人ACE2结合的能力。我们鉴定出56种抑制结合率<90%的化合物，测量了结合抑制的半数有效浓度（EC），并通过计算模拟了最佳抑制剂与刺突蛋白和ACE2的对接。这些结果突出了一种有效的筛选方法，可用于识别能够破坏刺突蛋白-ACE2相互作用的化合物，以及识别几种潜在抑制剂，这些抑制剂可作为未来药物研发工作的模板。
