# Evaluation of artificial intelligence identified ipratropium bromide for the treatment of coronavirus disease 2019

**Authors:** Dong-Sub Jung, Seungwoo Cheon, Choon-Mee Kim, Jun-Won Seo, So Jung Sung, Da-Young Kim, Jae-Hak Lee, Wonwoo Kim, Jihoon Kang, Na-Ra Yun, Yi Rang Kim, Dong-Min Kim

PMC · DOI: 10.1038/s41598-025-27869-y · Scientific Reports · 2026-02-19

## TL;DR

This study evaluates ipratropium bromide, identified via AI, for treating severe COVID-19 in hamsters, showing promising results in reducing mortality and inflammation.

## Contribution

The novel use of AI to identify ipratropium bromide as a potential treatment for severe COVID-19 is presented.

## Key findings

- Ipratropium bromide treatment significantly reduced mortality in hamsters with severe COVID-19.
- IB-treated hamsters showed lower D-dimer levels and reduced lung inflammation compared to controls.
- Combination therapy with IB and remdesivir showed similar benefits to IB alone.

## Abstract

Ipratropium bromide (IB), identified through an artificial intelligence (AI)-aided drug screening platform, was evaluated for its safety and efficacy in treating severe coronavirus disease 2019 (COVID-19) using a hamster model in this study. The mortality rates in the vehicle, remdesivir-treated, IB-treated, and IB-remdesivir combination treatment groups were 70%, 15%, 5%, and 50%, respectively. The IB-treated group showed significantly lower blood D-dimer levels and fibrin degradation product when compared to that in the vehicle group, indicating prevention of thrombosis-related complications. Histological examination also revealed reduced lung inflammation in the IB and combination groups, compared to that in the vehicle and remdesivir groups, with fewer neutrophils in bronchoalveolar lavage fluid. Moreover, IB may prevent thrombosis-related complications caused by severe COVID-19.

The online version contains supplementary material available at 10.1038/s41598-025-27869-y.

## Linked entities

- **Chemicals:** ipratropium bromide (PubChem CID 31098), remdesivir (PubChem CID 121304016)
- **Diseases:** coronavirus disease 2019 (MONDO:0100096)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, OTOR (otoraplin) [NCBI Gene 56914] {aka FDP, MIAL1}, RPTOR (regulatory associated protein of MTOR complex 1) [NCBI Gene 57521] {aka KOG1, Mip1}, TMPRSS2 (transmembrane serine protease 2) [NCBI Gene 7113] {aka PRSS10}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** cough (MESH:D003371), deep vein thrombosis (MESH:D020246), cytotoxicity (MESH:D064420), weight loss (MESH:D015431), COVID-19 (MESH:D000086382), chills (MESH:D023341), ischemic stroke (MESH:D002544), myocardial infarction (MESH:D009203), infection (MESH:D007239), viral infection (MESH:D014777), death (MESH:D003643), thrombosis (MESH:D013927), hypothermia (MESH:D007035), infectious diseases (MESH:D003141), interstitial pneumonia (MESH:D017563), asthma (MESH:D001249), lung injuries (MESH:D055370), dyspnea (MESH:D004417), respiratory illness (MESH:D012140), Inflammation (MESH:D007249), hypoxia (MESH:D000860), respiratory distress (MESH:D012128), Fever (MESH:D005334), pulmonary embolism (MESH:D011655), lung inflammation (MESH:D011014), COPD (MESH:D029424), tachycardia (MESH:D013610)
- **Chemicals:** penicillin (MESH:D010406), Hematoxylin (MESH:D006416), H&amp;E (MESH:D006371), DMEM (-), IB (MESH:D009241), formalin (MESH:D005557), DMSO (MESH:D004121), eosin (MESH:D004801), CO2 (MESH:D002245), streptomycin (MESH:D013307), Remdesivir (MESH:C000606551), xylene (MESH:D014992), TC (MESH:D013667), saline (MESH:D012965), paraffin (MESH:D010232), ethanol (MESH:D000431), biotin (MESH:D001710), atropine (MESH:D001285), Acetylcholine (MESH:D000109), isoflurane (MESH:D007530), water (MESH:D014867), Giemsa (MESH:D001399)
- **Species:** Homo sapiens (human, species) [taxon 9606], Cricetinae (hamsters, subfamily) [taxon 10026], Cricetus cricetus (black-bellied hamster, species) [taxon 10034], Severe acute respiratory syndrome-related coronavirus (no rank) [taxon 694009], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Gammacoronavirus (genus) [taxon 694013]
- **Cell lines:** THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), Vero — Chlorocebus sabaeus (Green monkey), Spontaneously immortalized cell line (CVCL_0059), SH101 — Homo sapiens (Human), Gastric tubular adenocarcinoma, Cancer cell line (CVCL_RT29), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920905/full.md

## References

4 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920905/full.md

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Source: https://tomesphere.com/paper/PMC12920905