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In silico analysis of the impact of toxic metals on COVID-19 complications: molecular insights

Jovana Živanović
Jovana Živanović
, 
Katarina Baralić
Katarina Baralić
, 
Katarina Živančević
Katarina Živančević
, 
Dragica Božić
Dragica Božić
, 
Đurđica Marić
Đurđica Marić
, 
Evica Antonijević Miljaković
Evica Antonijević Miljaković
, 
Aleksandra Buha Đorđević
Aleksandra Buha Đorđević
, 
Marijana Ćurčić
Marijana Ćurčić
, 
Zorica Bulat
Zorica Bulat
, 
Biljana Antonijević
Biljana Antonijević
 et 
Danijela Đukić-Ćosić
Danijela Đukić-Ćosić
   | 29 juin 2024
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Article Category: Original article
Publié en ligne: 29 juin 2024
Pages: 102 - 109
Reçu: 01 janv. 2024
Accepté: 01 mai 2024
DOI: https://doi.org/10.2478/aiht-2024-75-3819
Mots clés
© 2024 Jovana Živanović et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Flow chart of the steps used to analyse the association between exposure to toxic metals and COVID-19 complications
Flow chart of the steps used to analyse the association between exposure to toxic metals and COVID-19 complications

Figure 2

Network of five genes/proteins associated with the development of COVID-19 and affected by As, Cd, Pb, Hg, Ni, and Cr and their relationship with 20 genes/proteins, identified by the GeneMANIA prediction tool (https://genemania.org). Legend: pink lines – physical interactions; purple lines – co-expression; orange lines – server-predicted interactions; blue lines – co-localisation; green lines – genetic interactions; light blue lines – shared pathway; gray-yellow lines – shared protein domains
Network of five genes/proteins associated with the development of COVID-19 and affected by As, Cd, Pb, Hg, Ni, and Cr and their relationship with 20 genes/proteins, identified by the GeneMANIA prediction tool (https://genemania.org). Legend: pink lines – physical interactions; purple lines – co-expression; orange lines – server-predicted interactions; blue lines – co-localisation; green lines – genetic interactions; light blue lines – shared pathway; gray-yellow lines – shared protein domains

Figure 3

Networks of five genes/proteins associated with the development of COVID-19 and the 20 related genes for each toxic metal separately. Legend: pink lines – physical interactions; purple lines – co-expression; orange lines – server-predicted interactions; blue lines – co-localisation; green lines – genetic interactions; light blue lines – shared pathway; gray-yellow lines – shared protein domains
Networks of five genes/proteins associated with the development of COVID-19 and the 20 related genes for each toxic metal separately. Legend: pink lines – physical interactions; purple lines – co-expression; orange lines – server-predicted interactions; blue lines – co-localisation; green lines – genetic interactions; light blue lines – shared pathway; gray-yellow lines – shared protein domains

Correlation of the 25 identified genes (five common and 20 related) with biological processes, molecular functions, pathways, and diseases associated with COVID-19 complications

Category Name ID p-value Genes involved*
Molecular function cytokine binding GO:0019955 1.341E-17 11
cytokine receptor binding GO:0005126 2.170E-17 13
cytokine activity GO:0005125 3.580E-15 11
signalling receptor binding GO:0005102 1.187E-11 16
receptor ligand activity GO:0048018 1.952E-11 11
Biological process inflammatory response GO:0006954 4.830E-28 23
cytokine-mediated signalling pathway GO:0019221 1.992E-25 19
cellular response to cytokine stimulus GO:0071345 1.277E-20 19
response to cytokine GO:0034097 9.706E-20 19
leukocyte migration GO:0050900 8.016E-19 15
Pathway KEGG cytokine receptor interaction M9809 1.039E-30 20
reactome interleukin 10 signalling M27605 6.459E-22 11
reactome signalling by interleukins M874 4.294E-18 16
WP SARSCOV2 innate immunity evasion and cell-specific immune response M40067 9.207E-18 10
WP overview of proinflammatory and profibrotic mediators M42533 1.091E-16 11
Disease susceptibility to HIV infection 609423 6.577E-6 3
malaria, susceptibility to cv:C1836230 6.577E-6 3
white blood cell count quantitative trait locus 1 611162 5.893E-4 2
WHIM syndrome 2 cv:C1970028 5.893E-4 2
Graft-versus-host disease, susceptibility to 611862 2.333E-3 1

Effects of As, Cd, Pb, Hg, Ni, and Cr on common genes

Toxic metals Interactions CXCL8 IL10 IL1B IL6 TNF
As Expression of mRNA N/A ↓ ↓↑ ↑ ↓
Protein expression ↑ ↑ ↓↑ ↑ ↓↑
Cd Expression of mRNA ↑ ↓ ↓↑ ↓↑ ↓↑
Protein expression ↑ ↑ ↑ ↑ ↑
Pb Expression of mRNA ↑ N/A ↑ N/A ↑
Protein expression ↑ ↓↑ ↑ ↑ ↑
Hg Expression of mRNA N/A ↑ ↑ N/A ↑
Protein expression ↑ N/A ↑ ↑ ↑
Ni Expression of mRNA ↑ ↑ ↑ ↑ ↑
Protein expression ↑ N/A ↑ ↑ ↑
Cr Expression of mRNA ↑ N/A N/A N/A ↑
Protein expression N/A N/A N/A ↓ ↑

Genes associated with COVID-19 and the investigated metals (CTD: https://ctdbase.org/)

Toxic metals Total number of genes Genes associated with COVID-19
Arsenic (As) 4997 ATP11A, BCL11A, CCL2, CCL3, CCR2, CRP, CXCL8, ICAM5, IFNAR2, IL10, IL10RB, IL1B, IL2, IL2RA, IL6, IL7, LZTFL1, MUC1, OAS1, TNF
Cadmium (Cd) 5281 AGT, CCL2, CCR2, CD209, CRP, CXCL8, F8, HCK, IL10, IL1B, IL2, IL6, IL7, MUC1, OAS1, SELE, TNF, UGCG
Lead (Pb) 3278 AGT, BSG, CCL2, CCL3, CD209, CRP, CXCL10, CXCL8, ICAM5, IL10, IL1B, IL6, TNF
Mercury (Hg) 635 CCL3, CCR2, CRP, CXCL8, IL10, IL1B, IL2, IL6, TNF, UGCG
Nickel (Ni) 7665 ACE2, AGT, BCL11A, BTK, CCL2, CCL3, CCR2, CD209, CRP, CXCL10, CXCL8, FUT2, HCK, IFNAR2, IL10, IL10RB, IL1B, IL2, IL2RA, IL6, IL7, OAS1, PLSCR1, SELE, TMPRSS2, TMPRSS4, TNF
Chromium (Cr) 2353 AGT, CXCL8, IL10, IL1B, IL6, TNF, UGCG
As+Cd+Pb+Hg+Ni+Cr 5 CXCL8, IL10, IL1B, IL6, TNF
eISSN:
1848-6312
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Anglais, Slovenian
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Medicine, Basic Medical Science, other
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