Theoretical Study of the Molecular Mechanism of Maxingyigan Decoction Against COVID-19: Network Pharmacology-based Strategy

Abstract

Aim and Objective: 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. Methods: A network pharmacology strategy involving drug-likeness evaluation, prediction of oral bioavailability, network analyses, and virtual molecular docking were used to predict the mechanism of action of MXYG against COVID-19. Results: 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. Conclusion: The hub genes of COVID-19 helped to reveal the underlying pathogenesis and therapeutic targets of COVID19. This study represents the first report on the molecular mechanism of MXYG decoction against COVID-19.

Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies

“…Three of the studies evaluated for data extraction (Glinsky [40], Ruan et al [41] Wang et al [42]) used some flavonoids to build molecular maps guided by genomic regulatory elements by analyzing gene silencing and overexpression experiments. Quercetin was a flavonoid identified as a supposed mitigation agent for COVID-19.…”

Analysis of the mechanism of Shufeng Jiedu capsule prevention and treatment for COVID-19 by network pharmacology tools

“… Mechanisms: 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. [59] Cold-Damp Plague Formula TCMSP; TCMID; Swiss ADME; STITCH; GeneCards; STRING; Cytoscape; Key targets: IL6, TNF, IL10, MAPK8, MAPK3, CXCL8, CASP3, PTGS2, TP53, and MAPK1. KEGG signaling pathways: TNF signaling pathway, MAPK signaling pathway, Fc epsilon RI signaling pathway, toxoplasmosis, leishmaniasis, and so on.…”

Application of network pharmacology in the study of the mechanism of action of traditional chinese medicine in the treatment of COVID-19

“…Different from this, some scholars have found that Maxingyigan Decoction (MXYGD) for the treatment of COVID-19 contains three key components quercetin, luteolin, and formononetin, and also has three pivotal target genes, namely IL4, IL6, and CASP3, the results of molecular docking validation showed that the IL6 receptor and quercetin had the highest docking score, and the other three key components scored higher than Ribavirin. MXYGD plays an important role in the treatment and prevention of COVID-19 by activating leukocytes, T cells, lymphocytes, and other immune and anti-inflammatory effects ( Wang, et al, 2021b ). Today, Lianhua Qingwen Capsule has achieved good efficacy in the clinical treatment of COVID-19, which is also recognized by many scholars around the world ( Zheng, et al, 2020a ).…”