Delhi Pharmaceutical Sciences and Research University, New Delhi - 110017, Delhi, India.
Institute of Pharmacy, Nirma University, Ahmedabad - 382481, Gujarat, India.
Rev Cardiovasc Med. 2020 Sep 30;21(3):365-384. doi: 10.31083/j.rcm.2020.03.118.
Angiotensin-converting enzyme 2 (ACE2), the host cell-binding site for SAR-CoV-2, poses two-fold drug development problems. First, the role of ACE2 itself is still a matter of investigation, and no specific drugs are available targeting ACE2. Second, as a consequence of SARS-CoV-2 interaction with ACE2, there is an impairment of the renin-angiotensin system (RAS) involved in the functioning of vital organs like the heart, kidney, brain, and lungs. In developing antiviral drugs for COVID-19, ACE2, RNA-dependent RNA polymerase (RdRp), and the specific enzymes involved in the viral and cellular gene expression have been the primary targets. SARS-CoV-2 being a new virus with unusually high mortality, there has been a need to get medicines in an emergency, and the drug repurposing has been a primary strategy. Considering extensive mortality and morbidity throughout the world, we have made a maiden attempt to discover the drugs interacting with RAS and identify the lead compounds from herbal plants using molecular docking. Both host ACE2 and viral RNA-dependent RNA polymerase (RdRp) and ORF8 appear to be the primary targets for the treatment of COVID-19. While the drug repurposing of currently approved drugs seems to be one strategy for the treatment of COVID-19, purposing phytochemicals may be another essential strategy for discovering lead compounds. Using molecular docking, we have identified a few phytochemicals that may provide insights into designing herbal and synthetic therapeutics to treat COVID-19.
血管紧张素转换酶 2（ACE2）是 SARS-CoV-2 的宿主细胞结合位点，这给药物研发带来了双重挑战。首先，ACE2 本身的作用仍在研究之中，尚无针对 ACE2 的特定药物。其次，由于 SARS-CoV-2 与 ACE2 的相互作用，肾素-血管紧张素系统（RAS）受到损害，而 RAS 参与心脏、肾脏、大脑和肺部等重要器官的功能。在开发用于治疗 COVID-19 的抗病毒药物时，ACE2、RNA 依赖性 RNA 聚合酶（RdRp）以及涉及病毒和细胞基因表达的特定酶一直是主要目标。由于 SARS-CoV-2 是一种死亡率异常高的新型病毒，因此需要紧急获得药物，药物重定位已成为主要策略。考虑到全球范围内广泛的死亡率和发病率，我们首次尝试使用分子对接来发现与 RAS 相互作用的药物，并从草药植物中鉴定出先导化合物。宿主 ACE2 和病毒 RNA 依赖性 RNA 聚合酶（RdRp）和 ORF8 似乎都是治疗 COVID-19 的主要靶标。虽然对现有批准药物的重新定位似乎是治疗 COVID-19 的一种策略，但植物化学物质的重新定位可能是发现先导化合物的另一种重要策略。通过分子对接，我们已经确定了一些可能为设计治疗 COVID-19 的草药和合成疗法提供思路的植物化学物质。
