Table4_Network Pharmacology and Bioinformatics Analyses Identify Intersection Genes of Vitamin D3 and COVID-19 as Potential Therapeutic Targets.pdf

Purpose: The persistent pandemic of coronavirus disease 2019 (COVID-19), the discovery of gastrointestinal transmission routes and the possible susceptibility of cancer patients to COVID-19 have forced us to search for effective pathways against stomach adenocarcinoma (STAD)/COVID-19. Vitamin D3 (VD3) is a steroid hormone with antiviral, anti-inflammatory and immunomodulatory properties. This study aimed to evaluate the possible functional role and potential mechanisms of action of VD3 as an anti-COVID-19 and anti- STAD.
Methods: Clinicopathological analysis, enrichment analysis and protein interaction analysis using bioinformatics and network pharmacology methods. Validate the binding activity of VD3 to core pharmacological targets and viral crystal structures using molecular docking.
Results: We revealed the clinical characteristics of STAD/COVID-19 patients. We also demonstrated that VD3 may be anti- STAD/COVID-19 through antiviral, anti-inflammatory, and immunomodulatory pathways. Molecular docking results showed that VD3 binds well to the relevant targets of COVID-19, including the spike RBD/ACE2 complex and main protease (Mpro, also known as 3CLpro). We also identified five core pharmacological targets of VD3 in anti-STAD/COVID-19 and validated the binding activity of VD3 to PAI1 by molecular docking.
Conclusion: This study reveals for the first time that VD3 may act on disease target gene SERPINE1 through inflammatory and viral related signaling pathways and biological functions for the therapy of STAD/COVID-19. This may provide a new idea for the use of VD3 in the treatment of STAD/COVID-19.

研究背景与目的：持续蔓延的新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）大流行、胃肠道传播途径的发现，以及癌症患者对COVID-19的易感风险，促使我们探寻针对胃腺癌（stomach adenocarcinoma, STAD）合并COVID-19的有效干预途径。维生素D3（Vitamin D3, VD3）是一种具有抗病毒、抗炎及免疫调节特性的类固醇激素。本研究旨在评估VD3作为抗COVID-19及抗STAD药物的潜在功能作用与作用机制。
研究方法：本研究采用生物信息学与网络药理学方法开展临床病理分析、富集分析及蛋白质相互作用分析；通过分子对接技术验证VD3与核心药理靶点及病毒晶体结构的结合活性。
研究结果：本研究阐明了STAD合并COVID-19患者的临床特征；证实VD3可通过抗病毒、抗炎及免疫调节途径发挥抗STAD/COVID-19作用。分子对接结果显示，VD3可与COVID-19相关靶点高效结合，包括spike RBD/ACE2复合物及主要蛋白酶（Mpro，又称3CLpro）。本研究同时鉴定出VD3发挥抗STAD/COVID-19作用的5个核心药理靶点，并通过分子对接验证了VD3与PAI1的结合活性。
研究结论：本研究首次揭示，VD3可通过炎症及病毒相关信号通路与生物学功能，作用于疾病靶基因SERPINE1，从而实现STAD/COVID-19的治疗。该研究为VD3应用于STAD/COVID-19的治疗提供了全新的思路。