Human Nutraceuticals and Bioinformatics Research Unit, Department of Biochemistry, Salem University, Lokoja, Nigeria.
Department of Biochemistry, Bingham University, Karu, Nigeria.
Antivir Chem Chemother. 2020 Jan-Dec;28:2040206620984076. doi: 10.1177/2040206620984076.
Corona Virus Disease 2019 (COVID-19) is a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Exploiting the potentials of phytocompounds is an integral component of the international response to this pandemic. In this study, a virtual screening through molecular docking analysis was used to screen a total of 226 bioactive compounds from African herbs and medicinal plants for direct interactions with SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). From these, 36 phytocompounds with binding affinities higher than the approved reference drugs (remdesivir and sobosivir), were further docked targeting the active sites of SARS-CoV-2, as well as SARS-CoV and HCV RdRp. A hit list of 7 compounds alongside two positive controls (remdesivir and sofosbuvir) and two negative controls (cinnamaldehyde and Thymoquinone) were further docked into the active site of 8 different conformations of SARS-CoV-2 RdRp gotten from molecular dynamics simulation (MDS) system equilibration. The top docked compounds were further subjected to predictive druglikeness and ADME/tox filtering analyses. Drugable alkaloids (10'-hydroxyusambarensine, cryptospirolepine, strychnopentamine) and flavonoids (usararotenoid A, and 12α-epi-millettosin), were reported to exhibit strong affinity binding and interactions with key amino acid residues in the catalytic site, the divalent-cation-binding site, and the NTP entry channel in the active region of the RdRp enzyme as the positive controls. These phytochemicals, in addition to other promising antivirals such as remdesivir and sofosbuvir, may be exploited towards the development of a cocktail of anti-coronavirus treatments in COVID-19. Experimental studies are recommended to validate these study.
2019 年冠状病毒病（COVID-19）是由严重急性呼吸系统综合症冠状病毒 2 型（SARS-CoV-2）引起的大流行。利用植物化合物的潜力是应对这一大流行的国际反应的一个组成部分。在这项研究中，通过分子对接分析进行了虚拟筛选，以筛选来自非洲草药和药用植物的总共 226 种生物活性化合物，以寻找与 SARS-CoV-2 RNA 依赖性 RNA 聚合酶（RdRp）的直接相互作用。在这些化合物中，有 36 种植物化合物的结合亲和力高于已批准的参考药物（瑞德西韦和索布韦），进一步针对 SARS-CoV-2、SARS-CoV 和 HCV RdRp 的活性部位进行对接。对来自分子动力学模拟（MDS）系统平衡的 8 种不同构象的 SARS-CoV-2 RdRp 的活性部位，进一步对接了 7 种化合物的命中列表以及 2 种阳性对照（瑞德西韦和索布韦）和 2 种阴性对照（肉桂醛和百里醌）。对顶级对接化合物进行了进一步的预测药物相似性和 ADME/tox 过滤分析。报道具有强亲和力结合和与催化部位、二价阳离子结合部位以及活性区域中 RdRp 酶的 NTP 进入通道中的关键氨基酸残基相互作用的药物生物碱（10'-羟基乌巴伦辛、隐螺色胺、士的宁戊胺）和类黄酮（usararotenoid A 和 12α-表-米列托辛）作为阳性对照。除了瑞德西韦和索布韦等其他有前途的抗病毒药物外，这些植物化学物质可能被开发用于治疗 COVID-19 的冠状病毒鸡尾酒疗法。建议进行实验研究来验证这些研究。
