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 (M^pro). M^pro 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 M^pro 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, M^pro 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/<i>T</i>-test, biological activities using <i>in silico</i> 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型（SARS-CoV-2）引发的传染性大流行性疾病。SARS-CoV-2的关键组分为刺突蛋白（spike protein，S蛋白）与主蛋白酶（main protease，M^pro）。M^pro是病毒复制与转录过程中涉及的多种多聚蛋白成熟过程所必需的蛋白酶。S蛋白可帮助SARS-CoV-2通过血管紧张素转换酶2（angiotensin-converting enzyme 2，ACE2）侵入宿主细胞。由于ACE2是SARS-CoV-2结合宿主细胞的必需受体，除S蛋白与M^pro调节剂外，ACE2抑制剂与阻断剂也作为COVID-19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COVID-19的理想治疗潜力。本研究旨在评估传统药用植物针对COVID-19的治疗潜力。研究人员通过分子对接结合分子动力学模拟，对药用植物来源的生物活性成分及标准药物进行筛选，以考察其与S蛋白、M^pro及ACE2靶点的结合能力。基于相较于标准药物更高的结合亲和力，筛选得到部分生物活性成分，并进一步通过计算机模拟（in silico）工具分析其类药性（drug-likeness）、ADME/T试验等药理学特性与生物学活性。分析结果显示，多种生物活性成分与靶点蛋白的结合能与标准药物相当，甚至更优。基于Lipinski规则（Lipinski factors）及更低的结合能，最终选取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。结果表明，所选生物活性成分毒性较低、胃肠道吸收率更高，且针对COVID-19靶点展现出强效的抗炎与抗病毒活性。因此，这些药用植物来源的生物活性成分可进一步开发为植物药（phytopharmaceuticals），用于COVID-19的有效治疗。本文由Ramaswamy H. Sarma通讯供稿。传统药用植物来源的生物活性成分可潜在抑制SARS-CoV-2的蛋白靶点。本计算生物学研究证实，所筛选的药用植物生物活性成分具备针对COVID-19的最优药理学与生物学活性。