Identification of Drug Repurposing Candidates for Coxsackievirus B3 Infection in iPSC-Derived Brain-like Endothelial Cells Article Swipe
Jacob F. Wood
,
John Vergis
,
Ali Sajid Imami
,
William G. Ryan
,
Jon Sin
,
Brandon J. Kim
,
Isaac T. Schiefer
,
Robert E. McCullumsmith
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/ijms26157041
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/ijms26157041
The enterovirus Coxsackievirus B3 causes a range of serious health problems, including aseptic meningitis, myocarditis, and pancreatitis. Currently, Coxsackievirus B3 has no targeted antiviral treatments or vaccines, leaving supportive care as the primary management option. Understanding how Coxsackievirus B3 interacts with and alters the blood–brain barrier may help identify new therapies to combat this often-devastating infection. We reanalyzed a previously published RNA sequencing dataset for Coxsackievirus B3-infected human-induced pluripotent stem-cell-derived brain endothelial cells (iBECs) to examine how Coxsackievirus B3 altered mRNA expression. By integrating GSEA, EnrichR, and iLINCs-based perturbagen analysis, we present a novel, systems-level approach to uncover potential drug repurposing candidates for CVB3 infection. We found dynamic changes in host transcriptomic response to Coxsackievirus B3 infection at 2- and 5-day infection time points. Downregulated pathways included ribosomal biogenesis and protein synthesis, while upregulated pathways included a defense response to viruses, and interferon production. Using iLINCs transcriptomic analysis, MEK, PDGFR, and VEGF inhibitors were identified as possible novel antiviral therapeutics. Our findings further elucidate Coxsackievirus B3-associated pathways in (iBECs) and highlight potential drug repurposing candidates, including pelitinib and neratinib, which may disrupt Coxsackievirus B3 pathology at the blood–brain barrier (BBB).
Related Topics
Concepts
Coxsackievirus
Drug repositioning
Enterovirus 71
Aseptic meningitis
Medicine
Biology
Myocarditis
Chemokine
Enterovirus
Virology
Immunology
Drug
Inflammation
Virus
Meningitis
Pharmacology
Cardiology
Psychiatry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms26157041
- https://www.mdpi.com/1422-0067/26/15/7041/pdf?version=1753186304
- OA Status
- gold
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412557898
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4412557898Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms26157041Digital Object Identifier
- Title
-
Identification of Drug Repurposing Candidates for Coxsackievirus B3 Infection in iPSC-Derived Brain-like Endothelial CellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-07-22Full publication date if available
- Authors
-
Jacob F. Wood, John Vergis, Ali Sajid Imami, William G. Ryan, Jon Sin, Brandon J. Kim, Isaac T. Schiefer, Robert E. McCullumsmithList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms26157041Publisher landing page
- PDF URL
-
https://www.mdpi.com/1422-0067/26/15/7041/pdf?version=1753186304Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/1422-0067/26/15/7041/pdf?version=1753186304Direct OA link when available
- Concepts
-
Coxsackievirus, Drug repositioning, Enterovirus 71, Aseptic meningitis, Medicine, Biology, Myocarditis, Chemokine, Enterovirus, Virology, Immunology, Drug, Inflammation, Virus, Meningitis, Pharmacology, Cardiology, PsychiatryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
53Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.novel, | 93 |
| abstract_inverted_index.(iBECs) | 73, 168 |
| abstract_inverted_index.altered | 79 |
| abstract_inverted_index.aseptic | 12 |
| abstract_inverted_index.barrier | 45, 188 |
| abstract_inverted_index.changes | 108 |
| abstract_inverted_index.dataset | 63 |
| abstract_inverted_index.defense | 137 |
| abstract_inverted_index.disrupt | 181 |
| abstract_inverted_index.dynamic | 107 |
| abstract_inverted_index.examine | 75 |
| abstract_inverted_index.further | 162 |
| abstract_inverted_index.leaving | 27 |
| abstract_inverted_index.option. | 34 |
| abstract_inverted_index.points. | 123 |
| abstract_inverted_index.present | 91 |
| abstract_inverted_index.primary | 32 |
| abstract_inverted_index.protein | 130 |
| abstract_inverted_index.serious | 8 |
| abstract_inverted_index.uncover | 97 |
| abstract_inverted_index.EnrichR, | 85 |
| abstract_inverted_index.approach | 95 |
| abstract_inverted_index.findings | 161 |
| abstract_inverted_index.identify | 48 |
| abstract_inverted_index.included | 126, 135 |
| abstract_inverted_index.pathways | 125, 134, 166 |
| abstract_inverted_index.possible | 156 |
| abstract_inverted_index.response | 112, 138 |
| abstract_inverted_index.targeted | 22 |
| abstract_inverted_index.viruses, | 140 |
| abstract_inverted_index.analysis, | 89, 147 |
| abstract_inverted_index.antiviral | 23, 158 |
| abstract_inverted_index.elucidate | 163 |
| abstract_inverted_index.highlight | 170 |
| abstract_inverted_index.including | 11, 175 |
| abstract_inverted_index.infection | 116, 121 |
| abstract_inverted_index.interacts | 39 |
| abstract_inverted_index.pathology | 184 |
| abstract_inverted_index.pelitinib | 176 |
| abstract_inverted_index.potential | 98, 171 |
| abstract_inverted_index.problems, | 10 |
| abstract_inverted_index.published | 60 |
| abstract_inverted_index.ribosomal | 127 |
| abstract_inverted_index.therapies | 50 |
| abstract_inverted_index.vaccines, | 26 |
| abstract_inverted_index.Currently, | 17 |
| abstract_inverted_index.biogenesis | 128 |
| abstract_inverted_index.candidates | 101 |
| abstract_inverted_index.identified | 154 |
| abstract_inverted_index.infection. | 55, 104 |
| abstract_inverted_index.inhibitors | 152 |
| abstract_inverted_index.interferon | 142 |
| abstract_inverted_index.management | 33 |
| abstract_inverted_index.neratinib, | 178 |
| abstract_inverted_index.previously | 59 |
| abstract_inverted_index.reanalyzed | 57 |
| abstract_inverted_index.sequencing | 62 |
| abstract_inverted_index.supportive | 28 |
| abstract_inverted_index.synthesis, | 131 |
| abstract_inverted_index.treatments | 24 |
| abstract_inverted_index.B3-infected | 66 |
| abstract_inverted_index.candidates, | 174 |
| abstract_inverted_index.endothelial | 71 |
| abstract_inverted_index.enterovirus | 1 |
| abstract_inverted_index.expression. | 81 |
| abstract_inverted_index.integrating | 83 |
| abstract_inverted_index.meningitis, | 13 |
| abstract_inverted_index.perturbagen | 88 |
| abstract_inverted_index.pluripotent | 68 |
| abstract_inverted_index.production. | 143 |
| abstract_inverted_index.repurposing | 100, 173 |
| abstract_inverted_index.upregulated | 133 |
| abstract_inverted_index.iLINCs-based | 87 |
| abstract_inverted_index.myocarditis, | 14 |
| abstract_inverted_index.B3-associated | 165 |
| abstract_inverted_index.Downregulated | 124 |
| abstract_inverted_index.Understanding | 35 |
| abstract_inverted_index.blood–brain | 44, 187 |
| abstract_inverted_index.human-induced | 67 |
| abstract_inverted_index.pancreatitis. | 16 |
| abstract_inverted_index.systems-level | 94 |
| abstract_inverted_index.therapeutics. | 159 |
| abstract_inverted_index.Coxsackievirus | 2, 18, 37, 65, 77, 114, 164, 182 |
| abstract_inverted_index.transcriptomic | 111, 146 |
| abstract_inverted_index.often-devastating | 54 |
| abstract_inverted_index.stem-cell-derived | 69 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5048739282 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 8 |
| corresponding_institution_ids | https://openalex.org/I4210138764, https://openalex.org/I90871651 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8299999833106995 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.43751532 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |