Abstract

COVID-19 is a novel severe acute respiratory syndrome coronavirus. Currently, there is no effective treatment and vaccines seem to be the solution in the future. Virtual screening of potential drugs against the S protein of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has provided small molecular compounds with a high binding affinity. Unfortunately, most of these drugs do not attach with the binding interface of the receptor-binding domain (RBD)–angiotensin-converting enzyme-2 (ACE-2) complex in host cells. Molecular modeling was carried out to evaluate the potential antiviral properties of the components of the medicinal herb Uncaria tomentosa (cat’s claw) focusing on the binding interface of the RBD–ACE-2 and the viral spike protein. The in silico approach starts with protein–ligand docking of 26 Cat’s claw key components followed by molecular dynamics simulations and re-docked calculations. Finally, we carried out drug-likeness calculations for the most qualified cat’s claw components. The structural bioinformatics approaches led to the identification of several bioactive compounds of U. tomentosa with potential therapeutic effect by dual strong interaction with interface of the RBD–ACE-2 and the ACE-2 binding site on SARS-CoV-2 RBD viral spike. In addition, in silico drug-likeness indices for these components were calculated and showed good predicted therapeutic profiles of these phytochemicals found in U. tomentosa (cat’s claw). Our findings suggest the potential effectiveness of cat’s claw as complementary and/or alternative medicine for COVID-19 treatment.

Communicated by Ramaswamy H. Sarma

摘要

COVID-19 是一种新型严重急性呼吸综合征冠状病毒。目前，还没有有效的治疗方法，疫苗似乎是未来的解决方案。针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的 S 蛋白的潜在药物的虚拟筛选提供了具有高结合亲和力的小分子化合物。不幸的是，这些药物中的大多数不与宿主细胞中受体结合域 (RBD)-血管紧张素转换酶-2 (ACE-2) 复合物的结合界面结合。进行分子模型以评估药草毛钩藤的成分的潜在抗病毒特性（猫爪）专注于 RBD-ACE-2 和病毒刺突蛋白的结合界面。计算机模拟方法从 26 个 Cat's Claw 关键成分的蛋白质-配体对接开始，然后进行分子动力学模拟和重新对接计算。最后，我们对最合格的猫爪成分进行了药物相似度计算。结构生物信息学方法通过与 RBD-ACE-2 的界面和 SARS-CoV-2 RBD 病毒刺突上的 ACE-2 结合位点的双重强相互作用，鉴定了几种具有潜在治疗作用的毛茸茸生物活性化合物。此外，计算了这些成分的计算机模拟药物相似性指数，并显示了在毛茸茸中发现的这些植物化学物质的良好预测治疗概况（猫爪）。我们的研究结果表明猫爪作为 COVID-19 治疗的补充和/或替代药物的潜在有效性。

由 Ramaswamy H. Sarma 传达