Alibaba Business School, Hangzhou Normal University, Hangzhou, 310000, China.
Sci Rep. 2023 Apr 10;13(1):5844. doi: 10.1038/s41598-023-31380-7.
Licorice, a traditional Chinese medicine, has been widely used for the treatment of COVID-19, but all active compounds and corresponding targets are still not clear. Therefore, this study proposed a deep learning-based network pharmacology approach to identify more potential active compounds and targets of licorice. 4 compounds (quercetin, naringenin, liquiritigenin, and licoisoflavanone), 2 targets (SYK and JAK2) and the relevant pathways (P53, cAMP, and NF-kB) were predicted, which were confirmed by previous studies to be associated with SARS-CoV-2-infection. In addition, 2 new active compounds (glabrone and vestitol) and 2 new targets (PTEN and MAP3K8) were further validated by molecular docking and molecular dynamics simulations (simultaneous molecular dynamics), as well as the results showed that these active compounds bound well to COVID-19 related targets, including the main protease (Mpro), the spike protein (S-protein) and the angiotensin-converting enzyme 2 (ACE2). Overall, in this study, glabrone and vestitol from licorice were found to inhibit viral replication by inhibiting the activation of Mpro, S-protein and ACE2; related compounds in licorice may reduce the inflammatory response and inhibit apoptosis by acting on PTEN and MAP3K8. Therefore, licorice has been proposed as an effective candidate for the treatment of COVID-19 through PTEN, MAP3K8, Mpro, S-protein and ACE2.
甘草是一种传统中药，已被广泛用于治疗 COVID-19，但甘草的所有活性化合物和相应靶点仍不清楚。因此，本研究提出了一种基于深度学习的网络药理学方法，以鉴定更多潜在的甘草活性化合物和靶点。预测了 4 种化合物（槲皮素、柚皮素、甘草素和甘草异黄酮）、2 个靶点（SYK 和 JAK2）和相关途径（P53、cAMP 和 NF-kB），这些靶点先前的研究已证实与 SARS-CoV-2 感染有关。此外，通过分子对接和分子动力学模拟（同时分子动力学）进一步验证了 2 种新的活性化合物（glabrone 和 vestitol）和 2 种新的靶点（PTEN 和 MAP3K8），结果表明这些活性化合物与 COVID-19 相关靶点结合良好，包括主要蛋白酶（Mpro）、刺突蛋白（S 蛋白）和血管紧张素转化酶 2（ACE2）。总的来说，在这项研究中，发现甘草中的 glabrone 和 vestitol 通过抑制 Mpro、S 蛋白和 ACE2 的激活来抑制病毒复制；甘草中的相关化合物可能通过作用于 PTEN 和 MAP3K8 来减轻炎症反应并抑制细胞凋亡。因此，甘草已被提议通过 PTEN、MAP3K8、Mpro、S 蛋白和 ACE2 成为治疗 COVID-19 的有效候选药物。
