Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Comb Chem High Throughput Screen. 2021;24(2):294-305. doi: 10.2174/1386207323666200806164635.
Maxingyigan (MXYG) decoction is a traditional Chinese medicine (TCM) prescription. However, how MXYG acts against coronavirus disease 2019 (COVID-19) is not known. We investigated the active ingredients and the therapeutic targets of MXYG decoction against COVID-19.
A network pharmacology strategy involving drug-likeness evaluation, prediction of oral bioavailability, network analyses, and virtual molecular docking was used to predict the mechanism of action of MXYG against COVID-19.
Thirty-three core COVID-19-related targets were identified from 1023 gene targets through analyses of protein-protein interactions. Eighty-six active ingredients of MXYG decoction hit by 19 therapeutic targets were screened out by analyses of a compound-compound target network. Via network topology, three "hub" gene targets (interleukin (IL-6), caspase-3, IL-4) and three key components (quercetin, formononetin, luteolin) were recognized and verified by molecular docking. Compared with control compounds (ribavirin, arbidol), the docking score of quercetin to the IL-6 receptor was highest, with a score of 5. Furthermore, the scores of three key components to SARS-CoV-2 are large as 4, 5, and 5, respectively, which are even better than those of ribavirin at 3. Bioinformatics analyses revealed that MXYG could prevent and treat COVID-19 through anti-inflammatory and immunity-based actions involving activation of T cells, lymphocytes, and leukocytes, as well as cytokine-cytokine-receptor interaction, and chemokine signaling pathways.
The hub genes of COVID-19 helped to reveal the underlying pathogenesis and therapeutic targets of COVID-19. This study represents the first report on the molecular mechanism of MXYG decoction against COVID-19.
麻杏石甘汤是一种中药方剂。然而，麻杏石甘汤治疗 2019 年冠状病毒病（COVID-19）的机制尚不清楚。我们研究了麻杏石甘汤治疗 COVID-19 的活性成分和治疗靶点。
采用网络药理学策略，包括药物相似性评价、口服生物利用度预测、网络分析和虚拟分子对接，预测麻杏石甘汤治疗 COVID-19 的作用机制。
通过蛋白质-蛋白质相互作用分析，从 1023 个基因靶点中鉴定出 33 个与 COVID-19 相关的核心靶点。通过化合物-靶点网络分析，筛选出 19 个治疗靶点中 86 种麻杏石甘汤的活性成分。通过网络拓扑分析，识别并验证了三个“枢纽”基因靶点（白细胞介素（IL-6）、半胱天冬酶-3、IL-4）和三个关键成分（槲皮素、芒柄花素、木樨草素），并通过分子对接进行验证。与对照化合物（利巴韦林、阿比多尔）相比，槲皮素与白细胞介素 6 受体的对接评分最高，为 5 分。此外，三种关键成分与 SARS-CoV-2 的评分分别为 4、5 和 5，甚至优于利巴韦林的 3 分。生物信息学分析表明，麻杏石甘汤可通过抗炎和免疫作用，包括 T 细胞、淋巴细胞和白细胞的激活，以及细胞因子-细胞因子受体相互作用和趋化因子信号通路，预防和治疗 COVID-19。
COVID-19 的枢纽基因有助于揭示 COVID-19 的潜在发病机制和治疗靶点。本研究首次报道了麻杏石甘汤治疗 COVID-19 的分子机制。
