Traditional medicinal plants against replication, maturation and transmission targets of SARS-CoV-2: computational investigation

COVID-19 is an infectious pandemic caused by the SARS-CoV-2 virus. The critical components of SARS-CoV-2 are the spike protein (S-protein) and the main protease (Mpro). Mpro is required for the maturation of the various polyproteins involved in replication and transcription. S-protein helps the SARS-CoV-2 to enter the host cells through the angiotensin-converting enzyme 2 (ACE2). Since ACE2 is required for the binding of SARS-CoV-2 on the host cells, ACE2 inhibitors and blockers have got wider attention, in addition to S-protein and Mpro modulators as potential therapeutics for COVID-19. So far, no specific drugs have shown promising therapeutic potential against COVID-19. The current study was undertaken to evaluate the therapeutic potential of traditional medicinal plants against COVID-19. The bioactives from the medicinal plants, along with standard drugs, were screened for their binding against S-protein, Mpro and ACE2 targets using molecular docking followed by molecular dynamics. Based on the higher binding affinity compared with standard drugs, bioactives were selected and further analyzed for their pharmacological properties such as drug-likeness, ADME/T-test, biological activities using in silico tools. The binding energies of several bioactives analyzed with target proteins were relatively comparable and even better than the standard drugs. Based on Lipinski factors and lower binding energies, seven bioactives were further analyzed for their pharmacological and biological characteristics. The selected bioactives were found to have lower toxicity with a higher GI absorption rate and potent anti-inflammatory and anti-viral activities against targets of COVID-19. Therefore, the bioactives from these medicinal plants can be further developed as phytopharmaceuticals for the effective treatment of COVID-19.
Communicated by Ramaswamy H. Sarma
Traditional medicinal plant bioactives can potentially inhibit SARS-CoV-2 protein targets. Computational investigation revealed that selected medicinal plant bioactives have the optimal pharmacological and biological activities against COVID-19.

新型冠状病毒肺炎（COVID-19）是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引发的传染性大流行病。SARS-CoV-2的关键组成部分为刺突蛋白（S-protein）与主蛋白酶（Mpro）。主蛋白酶（Mpro）是参与病毒复制与转录过程的各类多聚蛋白成熟所必需的物质。刺突蛋白可协助SARS-CoV-2通过血管紧张素转换酶2（ACE2）侵染宿主细胞。由于ACE2是SARS-CoV-2结合宿主细胞的必需受体，除靶向S蛋白与Mpro的调节剂外，ACE2抑制剂与阻断剂也作为新型冠状病毒肺炎的潜在治疗手段受到广泛关注。截至目前，尚未有特效药物展现出针对新型冠状病毒肺炎的可靠治疗潜力。本研究旨在评估传统药用植物针对新型冠状病毒肺炎的治疗潜力。研究人员借助分子对接结合分子动力学模拟的方法，筛选了药用植物中的生物活性成分，并与标准药物一同测试其与S蛋白、Mpro及ACE2靶点的结合能力。相较于标准药物，部分生物活性成分展现出更高的结合亲和力，因此被选中并通过计算机虚拟（in silico）工具进一步分析其类药性、ADME/T试验、生物学活性等药理学特性。经分析，多款生物活性成分与靶标蛋白结合的结合能与标准药物相当，甚至更优。基于利普金斯基规则（Lipinski factors）与更低的结合能，研究人员选取7种生物活性成分开展进一步的药理学与生物学特性分析。结果显示，所选生物活性成分毒性较低，胃肠道吸收速率更高，且针对新型冠状病毒肺炎靶点具备强效抗炎与抗病毒活性。因此，这些药用植物中的生物活性成分可进一步开发为植物药（phytopharmaceuticals），用于新型冠状病毒肺炎的有效治疗。
由Ramaswamy H. Sarma通讯。
传统药用植物来源的生物活性成分可通过抑制SARS-CoV-2蛋白靶点发挥潜在作用。计算机模拟研究表明，筛选得到的药用植物生物活性成分具备针对新型冠状病毒肺炎的最优药理学与生物学活性。