Data_Sheet_1_Integrated bioinformatics and in silico approaches reveal the biological targets and molecular mechanisms of 1,25-dihydroxyvitamin D against COVID-19 and diabetes mellitus.zip

Coronavirus disease 2019 (COVID-19) and diabetes mellitus (DM) are two major diseases threatening human health. The susceptibility of DM patients to COVID-19 and their worse outcomes have forced us to explore efficient routes to combat COVID-19/DM. As the most active form of Vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) has been shown a beneficial effect in the treatment of COVID-19/DM. However, the anti-COVID-19/DM mechanisms of 1,25(OH)2D remain unclear. In this study, an approach combining network pharmacology and molecular docking was performed to reveal the potential hub target genes and underlying mechanisms of 1,25(OH)2D in the treatment of COVID-19/DM. The hub targets and interaction pathways related to 1,25(OH)2D were identified by integrating the key 1,25(OH)2D-target-signaling pathway-COVID-19/DM networks. Fifteen hub targets of 1,25(OH)2D against COVID-19DM were determined, including EGFR, PIK3R1, PIK3CA, STAT3, MAPK1, ESR1, HSP90AA1, LCK, MTOR, IGF1, AR, NFKB1, PIK3CB, PTPN1, and MAPK14. An enrichment analysis of the hub targets further revealed that the effect of 1,25(OH)2D against COVID-19/DM involved multiple biological processes, cellular components, molecular functions and biological signaling pathways. Molecular docking disclosed that 1,25(OH)2D docked nicely with the hub target proteins, including EGFR, PIK3R1, and PIK3CA. These findings suggested that the potential mechanisms of 1,25(OH)2D against COVID-19/DM may be related to multiple biological targets and biological signaling pathways.

2019冠状病毒病（COVID-19）与糖尿病（DM）是威胁人类健康的两大主要疾病。糖尿病患者对COVID-19的易感性以及感染后更差的预后，促使我们探索对抗COVID-19与糖尿病的有效途径。作为维生素D最具活性的形式，1,25-二羟维生素D[1,25(OH)2D]已被证实对COVID-19与糖尿病的治疗具有有益作用。然而，1,25(OH)2D对抗COVID-19与糖尿病的具体作用机制仍未阐明。本研究采用网络药理学与分子对接相结合的方法，旨在揭示1,25(OH)2D用于治疗COVID-19与糖尿病的潜在核心靶基因及潜在作用机制。通过整合关键的1,25(OH)2D-靶标-信号通路-COVID-19/糖尿病调控网络，本研究鉴定出与1,25(OH)2D相关的核心靶标及其相互作用通路。本研究确定了1,25(OH)2D对抗COVID-19与糖尿病的15个核心靶标，包括EGFR、PIK3R1、PIK3CA、STAT3、MAPK1、ESR1、HSP90AA1、LCK、MTOR、IGF1、AR、NFKB1、PIK3CB、PTPN1及MAPK14。对核心靶标的富集分析进一步揭示，1,25(OH)2D对抗COVID-19与糖尿病的作用涉及多种生物过程、细胞组分、分子功能及生物信号通路。分子对接实验结果显示，1,25(OH)2D可与核心靶标蛋白（包括EGFR、PIK3R1及PIK3CA）实现良好结合。上述研究结果表明，1,25(OH)2D对抗COVID-19与糖尿病的潜在作用机制可能与多个生物靶标及生物信号通路密切相关。