鉴定山奈酚为新型冠状病毒入侵抑制剂和 DL-精氨酸为新型冠状病毒复制抑制剂：来自印度传统医学的选定植物对 COVID-19 的基于网络药理学的体外研究。

Identification of Kaempferol as Viral Entry Inhibitor and DL-Arginine as Viral Replication Inhibitor from Selected Plants of Indian Traditional Medicine against COVID-19: An Guided in vitro Approach.

机构信息

Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682 041, India.

Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682 041, India.

出版信息

Curr Comput Aided Drug Des. 2023;19(4):313-323. doi: 10.2174/1573409919666230112123213.

DOI:10.2174/1573409919666230112123213

PMID:36635906

Abstract

BACKGROUND

Indian traditional medicinal plants are known for their great potential in combating viral diseases. Previously, we reported a systematic review approach of seven plausible traditional Indian medicinal plants against SARS-CoV-2.

METHODS

Molecular docking was conducted with Biovia Discovery Studio. Three binding domains for spike glycoprotein (PDB IDs: 6LZG, 6M17, 6M0J) and one binding domain of RdRp (PDB ID: 7BTF) were used. Among 100 phytoconstituents listed from seven plants by the IMPPAT database used for virtual screening, the best six compounds were again filtered using Swiss ADME prediction and Lipinski's rule. Additionally, a pseudovirion assay was performed to study the interaction of SARS-CoV-2 S1-protein with the ACE 2 receptor to further confirm the effect.

RESULTS

Chebulagic acid (52.06 Kcal/mol) and kaempferol (48.84 Kcal/mol) showed increased interaction energy compared to umifenovir (33.68 Kcal/mol) for the 6LZG binding domain of spike glycoprotein. Epicatechin gallate (36.95 Kcal/mol) and arachidic acid (26.09 Kcal/mol) showed equally comparable interaction energy compared to umifenovir (38.20 Kcal/mol) for the 6M17 binding domain of spike glycoprotein. Trihydroxychalcone (35.23 Kcal/mol) and kaempferol (36.96 Kcal/mol) showed equally comparable interaction energy with umifenovir (36.60 Kcal/mol) for 6M0J binding domain of spike glycoprotein. Upon analyzing the phytoconstituents against RdRp binding domain, DL-arginine (41.78 Kcal/mol) showed comparable results with the positive control remdesivir (47.61 Kcal/mol). ADME analysis performed using Swiss ADME revealed that kaempferol and DL arginine showed drug-like properties with appropriate pharmacokinetic parameters. Further in vitro analysis of kaempferol by pseudovirion assay confirmed an acceptable decrease of the lentiviral particles in transfected HEK293T-hACE2 cells.

CONCLUSION

The study highlights that kaempferol and DL-arginine could be the significant molecules to exhibit potent action against SARS-CoV-2 and its variants.

摘要

背景

印度传统药用植物因其在对抗病毒性疾病方面的巨大潜力而闻名。此前，我们报道了一种针对 SARS-CoV-2 的七种合理的印度传统药用植物的系统评价方法。

方法

使用 Biovia Discovery Studio 进行分子对接。使用了三个针对刺突糖蛋白的结合域（PDB ID：6LZG、6M17、6M0J）和一个针对 RdRp 的结合域（PDB ID：7BTF）。从 IMPPAT 数据库列出的七种植物中的 100 种植物成分中，使用瑞士 ADME 预测和 Lipinski 规则再次筛选出最好的六种化合物。此外，还进行了假病毒试验以研究 SARS-CoV-2 S1 蛋白与 ACE2 受体的相互作用，以进一步确认效果。

结果

与 umifenovir（33.68 Kcal/mol）相比，诃子酸（52.06 Kcal/mol）和山奈酚（48.84 Kcal/mol）在 6LZG 刺突糖蛋白结合域显示出增加的相互作用能。表儿茶素没食子酸酯（36.95 Kcal/mol）和花生四烯酸（26.09 Kcal/mol）在 6M17 刺突糖蛋白结合域与 umifenovir（38.20 Kcal/mol）表现出相当可比的相互作用能。三羟查耳酮（35.23 Kcal/mol）和山奈酚（36.96 Kcal/mol）在 6M0J 刺突糖蛋白结合域与 umifenovir（36.60 Kcal/mol）表现出相当可比的相互作用能。在分析针对 RdRp 结合域的植物成分时，DL-精氨酸（41.78 Kcal/mol）显示出与阳性对照瑞德西韦（47.61 Kcal/mol）相当的结果。使用瑞士 ADME 进行的 ADME 分析表明，山奈酚和 DL 精氨酸具有适当的药代动力学参数的类药性。进一步通过假病毒试验对山奈酚的体外分析证实，转染 HEK293T-hACE2 细胞的慢病毒颗粒有可接受的减少。