论文标题
针对RNA依赖RNA聚合酶的计算重新利用药物和天然产物作为潜在的COVID-19疗法
Computationally repurposed drugs and natural products against RNA dependent RNA polymerase as potential COVID-19 therapies
论文作者
论文摘要
为了快速开发COVID-19，只能使用药物（不使用标签）或已批准的天然产品，这些产品在以前的人类试验中已被注册或已被评估为安全。这些药物可以在COVID-19患者中快速评估，因为应该已经对其安全性和药代动力学进行了充分的理解。计算方法通过预测和对这些化合物对特定病毒蛋白靶标的亲和力进行预测和对潜在的SARS-COV-2活性的迅速筛查提供了希望。 RNA依赖性RNA聚合酶（RDRP）是SARS-COV-2药物开发的有希望的靶标，因为它没有人类同源物使RDRP抑制剂可能更安全，而靶向其他病毒蛋白的药物较少。我们将鲁棒的Vina对接在RDRP上结合在一起，与前80个鉴定的药物候选物的分子动力学（MD）模拟相结合，以产生最有希望的RDRP抑制剂列表。文献综述表明，许多预测的抑制剂已被证明在体外测定中具有活性，或者已预测其他组具有活性。现在，我们的屏幕揭示的新颖热门现在可以方便地测试RDRP抑制测定中的活性，如果在人类试验中进行测试之前，请在对抗病毒活性的测试中进行符合测试。
For fast development of COVID-19, it is only feasible to use drugs (off label use) or approved natural products that are already registered or been assessed for safety in previous human trials. These agents can be quickly assessed in COVID-19 patients, as their safety and pharmacokinetics should already be well understood. Computational methods offer promise for rapidly screening such products for potential SARS-CoV-2 activity by predicting and ranking the affinities of these compounds for specific virus protein targets. The RNA-dependent RNA polymerase (RdRP) is a promising target for SARS-CoV-2 drug development given it has no human homologs making RdRP inhibitors potentially safer, with fewer off-target effects that drugs targeting other viral proteins. We combined robust Vina docking on RdRP with molecular dynamic (MD) simulation of the top 80 identified drug candidates to yield a list of the most promising RdRP inhibitors. Literature reviews revealed that many of the predicted inhibitors had been shown to have activity in in vitro assays or had been predicted by other groups to have activity. The novel hits revealed by our screen can now be conveniently tested for activity in RdRP inhibition assays and if conformed testing for antiviral activity invitro before being tested in human trials
