Adegbola Peter Ifeoluwa, Semire Banjo, Fadahunsi Olumide Samuel, Adegoke Aanuoluwa Eunice
Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
Department of Pure and Applied Chemistry, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
Virusdisease. 2021 Mar;32(1):85-97. doi: 10.1007/s13337-021-00682-7. Epub 2021 Apr 10.
Plants are repository of important constituents with proven efficacy against many human diseases including viral diseases. The antiviral activity of many plants including and has been reported. The novel coronavirus disease is no exception among viral diseases in which plant compounds could serve as potent antagonist. Therefore, our study investigated the inhibitory potentials of and isolates against SARS-CoV-2 viral accessory proteins and the host serine protease. The protein data (SARS-CoV-2 Papain like protease (PLpro) (PDB: 6wx4), Chymotrypsin-like main protease (3CLpro) (PDB:6YB7), SARS-CoV nsp 12 (PDB: 6nus), Host cell protease (TMPRSS1) (PDB:5ce1) were obtained from the protein data bank (PDB), while the SDS format of each Ligands were obtained from Pubchem database. Molecular docking analysis was performed with Auto Dock Vina 1.5.6 and visualization of the interaction between the ligands and protein was done with discovery studio 2019. The ADMET prediction of pharmacokinetics and toxicity properties of the ligands was obtained using vNN Web Server. Our result showed that all the plant isolates demonstrated negative Gibb's free energy, indicating good binding affinity for both the viral and host protein. Overall, twenty-three of the forty-seven isolates showed good binding affinity comparable with dexamethasone that was used as reference drug. Although many of the compounds have good binding affinity for the viral and host proteins, based on the ADMET prediction, only Azadironic acid, Nimbionone, Nimbionol and Nimocinol all from could serve as potential drug candidate with good pharmacokinetics and toxicity profile. This study provides an insight into potential inhibitors and novel drug candidates for SARS-CoV-2. Further studies will look forward into the wet laboratory validation of Azadironic acid, Nimbionone, Nimbionol and Nimocinol against corona virus disease.
The online version contains supplementary material available at 10.1007/s13337-021-00682-7.
植物是重要成分的储存库，这些成分已被证明对包括病毒性疾病在内的许多人类疾病具有疗效。许多植物（包括[具体植物1]和[具体植物2]）的抗病毒活性已有报道。新型冠状病毒病在病毒性疾病中也不例外，植物化合物可作为有效的拮抗剂。因此？我们的研究调查了[具体植物1]和[具体植物2]的分离物对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒辅助蛋白和宿主丝氨酸蛋白酶的抑制潜力。蛋白质数据（SARS-CoV-2木瓜样蛋白酶（PLpro）（蛋白质数据银行（PDB）编号：6wx4）、胰凝乳蛋白酶样主要蛋白酶（3CLpro）（PDB编号：6YB7）、SARS-CoV非结构蛋白12（PDB编号：6nus）、宿主细胞蛋白酶（TMPRSS1）（PDB编号：5ce1））从蛋白质数据银行（PDB）获得，而每个配体的SDS格式从Pubchem数据库获得。使用Auto Dock Vina 1.5.6进行分子对接分析，并使用Discovery Studio 2019对配体与蛋白质之间的相互作用进行可视化。使用vNN网络服务器获得配体的药代动力学和毒性特性的ADMET预测。我们的结果表明，所有植物分离物均显示出负的吉布斯自由能，表明对病毒蛋白和宿主蛋白均具有良好的结合亲和力。总体而言，47种分离物中的23种显示出与用作参考药物的地塞米松相当的良好结合亲和力。尽管许多化合物对病毒蛋白和宿主蛋白具有良好的结合亲和力，但根据ADMET预测，只有均来自[具体植物1]的阿扎地ronic酸、Nimbionone、Nimbionol和Nimocinol可作为具有良好药代动力学和毒性特征的潜在药物候选物。本研究为SARS-CoV-2的潜在抑制剂和新型药物候选物提供了见解。进一步的研究将期待对阿扎地ronic酸、Nimbionone、Nimbionol和Nimocinol针对冠状病毒病进行湿实验室验证。
在线版本包含可在10.1007/s13337-021-00682-7获取的补充材料。
原文中“因此？”处疑似有信息缺失。
