# A dicoumarol-graphene oxide quantum dot polymer inhibits porcine reproductive and respiratory syndrome virus through the JAK-STAT signaling pathway

**Authors:** Zhuowei Li, Junjun Wang, Siyu Wang, Wei Zhao, Xiaolin Hou, Jianfang Wang, Hong Dong, Shuanghai Zhou, Yuan Gao, Wei Yao, Huanrong Li, Xuewei Liu

PMC · DOI: 10.3389/fmicb.2024.1417404 · Frontiers in Microbiology · 2024-06-19

## TL;DR

A new polymer made with dicoumarol and graphene oxide quantum dots shows promise in fighting a virus that causes major losses in the pig farming industry.

## Contribution

A novel dicoumarol-graphene oxide quantum dot polymer is shown to inhibit PRRSV by activating the JAK-STAT pathway.

## Key findings

- DIC-GQDs inhibit PRRSV replication and activate the JAK/STAT signaling pathway in porcine alveolar macrophages.
- DIC-GQDs alleviate clinical symptoms and pathological reactions in PRRSV-infected pigs.
- Transcriptome analysis shows upregulation of JAK1, STAT1, STAT2, IFN-β, and ISGs after DIC treatment.

## Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses in the global swine industry. The current vaccine options offer limited protection against PRRSV transmission, and there are no effective commercial antivirals available. Therefore, there is an urgent need to develop new antiviral strategies that slow global PRRSV transmission.

In this study, we synthesized a dicoumarol-graphene oxide quantum dot (DIC-GQD) polymer with excellent biocompatibility. This polymer was synthesized via an electrostatic adsorption method using the natural drug DIC and GQDs as raw materials.

Our findings demonstrated that DIC exhibits high anti-PRRSV activity by inhibiting the PRRSV replication stage. The transcriptome sequencing analysis revealed that DIC treatment stimulates genes associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway. In porcine alveolar macrophages (PAMs), DIC-GQDs induce TYK2, JAK1, STAT1, and STAT2 phosphorylation, leading to the upregulation of JAK1, STAT1, STAT2, interferon-β (IFN-β) and interferon-stimulated genes (ISGs). Animal challenge experiments further confirmed that DIC-GQDs effectively alleviated clinical symptoms and pathological reactions in the lungs, spleen, and lymph nodes of PRRSV-infected pigs.

These findings suggest that DIC-GQDs significantly inhibits PRRSV proliferation by activating the JAK/STAT signalling pathway. Therefore, DIC-GQDs hold promise as an alternative treatment for PRRSV infection.

## Linked entities

- **Genes:** TYK2 (tyrosine kinase 2) [NCBI Gene 7297], JAK1 (Janus kinase 1) [NCBI Gene 3716], STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772], STAT2 (signal transducer and activator of transcription 2) [NCBI Gene 6773]
- **Chemicals:** dicoumarol (PubChem CID 54676038)
- **Species:** Sus scrofa (taxon 9823)

## Full-text entities

- **Genes:** JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, STAT2 (signal transducer and activator of transcription 2) [NCBI Gene 6773] {aka IMD44, ISGF-3, P113, PTORCH3, STAT113}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, TYK2 (tyrosine kinase 2) [NCBI Gene 7297] {aka IMD35, JTK1}
- **Diseases:** infected (MESH:D007239), PRRSV infection (MESH:D019318)
- **Chemicals:** polymer (MESH:D011108), DIC (MESH:D003606), DIC-GQD (-)
- **Species:** Sus scrofa (pig, species) [taxon 9823], Porcine reproductive and respiratory syndrome virus (no rank) [taxon 28344]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11221364/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC11221364/full.md

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Source: https://tomesphere.com/paper/PMC11221364