Oh Ki-Kwang, Adnan Md
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Korea.
Curr Issues Mol Biol. 2022 Apr 19;44(5):1788-1809. doi: 10.3390/cimb44050123.
(LE) is known in Korean traditional medicine for its potent therapeutic effect and antiviral activity. Currently, coronavirus (COVID-19) disease is a developing global pandemic that can cause pneumonia. A precise study of the infection and molecular pathway of COVID-19 is therefore obviously important. The compounds of LE were identified from the Natural Product Activity and Species Source (NPASS) database and screened by SwissADME. The targets interacted with the compounds and were selected using the Similarity Ensemble Approach (SEA) and Swiss Target Prediction (STP) methods. PubChem was used to classify targets linked to COVID-19. The protein-protein interaction (PPI) networks and signaling pathways-targets-bioactive compounds (STB) networks were constructed by RPackage. Lastly, we performed the molecular docking test (MDT) to verify the binding affinity between significant complexes through AutoDock 1.5.6. The Natural Product Activity and Species Source (NPASS) revealed a total of 82 compounds from LE, which interacted with 1262 targets (SEA and STP), and 249 overlapping targets were identified. The 19 final overlapping targets from the 249 targets and 356 COVID-19 targets were ultimately selected. A bubble chart exhibited that inhibition of the MAPK signaling pathway could be a key mechanism of LE on COVID-19. The three key targets (RELA, TNF, and VEGFA) directly related to the MAPK signaling pathway, and methyl 4-prenyloxycinnamate, tormentic acid, and eugenol were related to each target and had the most stable binding affinity. The three bioactive effects on the three key targets might be synergistic effects to alleviate symptoms of COVID-19 infection. Overall, this study shows that LE can play a role in alleviating COVID-19 symptoms, revealing that the three components (bioactive compounds, targets, and mechanism) are the most significant elements of LE against COVID-19. However, the promising mechanism of LE on COVID-19 is only predicted on the basis of mining data; the efficacy of the chemical compounds and the affinity between compounds and the targets in experiment was ignored, which should be further substantiated through clinical trials.
在韩国传统医学中，刺蒺藜因其强大的治疗效果和抗病毒活性而闻名。目前，冠状病毒（COVID-19）疾病是一种正在全球范围内发展的大流行病，可导致肺炎。因此，对COVID-19的感染和分子途径进行精确研究显然很重要。从天然产物活性和物种来源（NPASS）数据库中鉴定出刺蒺藜的化合物，并通过SwissADME进行筛选。使用相似性集成方法（SEA）和瑞士靶点预测（STP）方法选择与这些化合物相互作用的靶点。利用PubChem对与COVID-19相关的靶点进行分类。通过R包构建蛋白质-蛋白质相互作用（PPI）网络和信号通路-靶点-生物活性化合物（STB）网络。最后，我们通过AutoDock 1.5.6进行分子对接试验（MDT），以验证重要复合物之间的结合亲和力。天然产物活性和物种来源（NPASS）显示刺蒺藜共有82种化合物，与1262个靶点相互作用（SEA和STP），并鉴定出249个重叠靶点。最终从249个靶点和356个COVID-19靶点中选择了19个最终重叠靶点。气泡图显示抑制丝裂原活化蛋白激酶（MAPK）信号通路可能是刺蒺藜对COVID-19发挥作用的关键机制。与MAPK信号通路直接相关的三个关键靶点（RELA、TNF和VEGFA），以及4-异戊烯氧基肉桂酸甲酯、山梨酸和丁香酚与每个靶点相关，且具有最稳定的结合亲和力。对这三个关键靶点的三种生物活性作用可能是协同作用，以减轻COVID-19感染的症状。总体而言，本研究表明刺蒺藜可在减轻COVID-19症状方面发挥作用，揭示了三种成分（生物活性化合物、靶点和机制）是刺蒺藜对抗COVID-19最重要的元素。然而，刺蒺藜对COVID-19的有前景的作用机制只是基于挖掘数据进行预测；忽略了化合物在实验中的疗效以及化合物与靶点之间的亲和力，这应通过临床试验进一步证实。
