Drug Screening for Autophagy Inhibitors Based on the Dissociation of Beclin1-Bcl2 Complex Using BiFC Technique and Mechanism of Eugenol on Anti-Influenza A Virus Activity
Open accessAbstract
Autophagy is involved in many human diseases, such as cancer, cardiovascular disease and virus infection, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), influenza A virus (IAV) and coxsackievirus B3/B4 (CVB3/B4), so a drug screening model targeting autophagy may be very useful for the therapy of these diseases. In our study, we established a drug screening model based on the inhibition of the dissociation of Beclin1-Bcl2 heterodimer, an important negative regulator of autophagy, using bimolecular fluorescence complementation (BiFC) technique for developing novel autophagy inhibitors and anti-IAV agents. From 86 examples of traditional Chinese medicines, we found Syzygium aromaticum L. had the best activity. We then determined the anti-autophagy and anti-IAV activity of eugenol, the major active compound of Syzygium aromaticum L., and explored its mechanism of action. Eugenol could inhibit autophagy and IAV replication, inhibited the activation of ERK, p38MAPK and IKK/NF-κB signal pathways and antagonized the effects of the activators of these pathways. Eugenol also ameliorated the oxidative stress and inhibited the expressions of autophagic genes. We speculated that the mechanism underlying might be that eugenol inhibited the oxidative stress and the activation of ERK1/2, p38MAPK and IKK/NF-κB pathways, subsequently inhibited the dissociation of Beclin1-Bcl2 heterodimer and autophagy, and finally impaired IAV replication. These results might conversely display the reasonableness of the design of our screening model. In conclusion, we have established a drug screening model for developing novel autophagy inhibitor, and find eugenol as a promising inhibitor for autophagy and IAV infection.
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CEO has shown antiviral activity against Ebola, influenza A virus, and herpes simplex virus types 1 and 2.
“CEO has shown antiviral activity against Ebola [111], influenza A virus [112], and herpes simplex virus types 1 and 2 [111].”
From Clove essential oil (Syzygium aromaticum L. Myrtaceae): Extraction, chemical composition, food applications, and essential bioactivity for human health (2021) · cites this paper as [112]
Citation [112] is attached only to the influenza A claim. The Results (page unavailable) report that eugenol inhibited influenza A virus replication, but the Materials and Methods identify the tested eugenol as a purchased compound; the paper does not establish antiviral activity for CEO itself. The Ebola and herpes simplex claims are attributed to [111], not this source. (LLM, conf=0.88)
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- Authors
- Dai, J.-P., Zhao, X.-F., Zeng, J., Wan, Q.-Y., Yang, J.-C., Li, W.-Z., Chen, X.-X., Wang, G.-F., & Li, K.-S.
- Affiliations
- Shantou University (CN)
- ORCID
- Zeng, Jun
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-16
- Volume
- 8
- Issue
- 4
- Pages
- e61026
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3628889
- OpenAlex
- W2169454801
- Cited by
- 123
- References
- 45
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 11 · 2022: 17 · 2021: 17 · 2020: 5 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 5 · 2015: 12 · 2014: 6 · 2013: 4
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (81172795, 81001322, 30972766, 31170852)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Keywords
- autophagy inhibitors, influenza A virus, eugenol, Syzygium aromaticum, traditional Chinese medicine, drug screening model, oxidative stress, ERK signaling, p38 MAPK signaling, IKK/NF-κB signaling, antiviral activity
- MeSH terms
- Antiviral Agents, Autophagy, Cell Line, Drug Evaluation, Preclinical, Drugs, Chinese Herbal, Eugenol, Humans, Influenza A virus, Syzygium
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