Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 2:9:1060095.
doi: 10.3389/fnut.2022.1060095. eCollection 2022.

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

Fanqiang Zeng  1 , Yongli Xu  2 , Chaoling Tang  3 , Zhigang Yan  2 , Chaohe Wei  1
Affiliations

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

Fanqiang Zeng et al. Front Nutr. .

Abstract

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.

Keywords: 1,25-dihydroxyvitamin D; COVID-19; bioinformatics; diabetes mellitus; molecular docking; network pharmacology.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The 2-dimensional structure of 1,25-dihydroxyvitamin D.
Figure 2
Figure 2
The flow-process diagram of the study.
Figure 3
Figure 3
Venn diagram of 1,25-dihydroxyvitamin D effects against COVID-19 and diabetes mellitus (DM) (A). Mutual target genes of 1,25-dihydroxyvitamin D and COVID-19/DM for constructing a protein–protein interaction network (B).
Figure 4
Figure 4
Protein–protein interaction networks and hub target genes. Hub target genes revealed in inner track. The darker the color, the higher the score.
Figure 5
Figure 5
Gene ontology enrichment analysis findings in 1,25-dihydroxyvitamin D against COVID-19/DM. Bar charts of biological processes, cellular components, and molecular functions (A), bubble chart of biological processes, cellular components, and molecular functions (B), circle chart of hub targets and biological processes (C).
Figure 6
Figure 6
Kyoto Encyclopedia of genes and genomes enrichment analysis findings in 1,25-dihydroxyvitamin D against COVID-19/DM. Bar chart of KEGG pathways (A), bubble chart of KEGG pathways (B), circle chart of hub targets and KEGG pathways (C).
Figure 7
Figure 7
1,25-dihydroxyvitamin D–targets–GO and KEGG pathways–COVID-19/DM network diagram.
Figure 8
Figure 8
Molecular docking details of the original ligands and 1,25-dihydroxyvitamin D to the target protein. 634-5HG8 (A), 1,25-dihydroxyvitamin D-5HG8 (B), 1LT-4JPS (C), 1,25-dihydroxyvitamin D-4JPS (D), P5J-6PYS (E), 1,25-dihydroxyvitamin D-6PYS (F).
Figure 9
Figure 9
The hydrophobic interactions of original ligands and 1,25-dihydroxyvitamin D with the target protein. Hydrophobic interactions are indicated by red opposite arcs. Hydrogen bonds are shown as green dashed lines. 634-5HG8 (A), 1,25-dihydroxyvitamin D-5HG8 (B), 1LT-4JPS (C), 1,25-dihydroxyvitamin D-4JPS (D), P5J-6PYS (E), 1,25-dihydroxyvitamin D-6PYS (F).
See this image and copyright information in PMC

References

    1. Käsk L, Larsen TH, Schjøtt J, Saeed S. The possibility of hypersensitivity myocarditis following COVID-19 vaccines: implications for contrast echocardiography. Cardiology. (2022) 147:417–8. 10.1159/000525349 - DOI - PubMed
    1. Kounis NG, Mplani V, Koniari I, Velissaris D. Hypersensitivity myocarditis and COVID-19 vaccines. Kardiol Pol. (2022) 80:109–10. 10.33963/KP.a2021.0166 - DOI - PubMed
    1. Wan EYF, Chui CSL, Lai FTT, Chan EWY, Li X, Yan VKC, et al. . Bell's palsy following vaccination with mRNA (BNT162B2) and inactivated (Coronavac) SARS-CoV-2 vaccines: a case series and nested case-control study. Lancet Infect Dis. (2022) 22:64–72. 10.1016/S1473-3099(21)00451-5 - DOI - PMC - PubMed
    1. National Institute for Health and Care Excellence: Guidelines . COVID-19 Rapid Guideline: Vaccine-Induced Immune Thrombocytopenia and Thrombosis (Vitt). London: National Institute for Health and Care Excellence (NICE) Copyright © NICE 2021. (2022). - PubMed
    1. Bilezikian JP, Bikle D, Hewison M, Lazaretti-Castro M, Formenti AM, Gupta A, et al. . Mechanisms in endocrinology: vitamin D and COVID-19. Eur J Endocrinol. (2020) 183:R133–r47. 10.1530/EJE-20-0665 - DOI - PMC - PubMed