Gemcitabine combined with baicalein exerts antiviral activity against PEDV by inhibiting the entry and replication phases

Abstract Cocktail therapy significantly reduces the development of resistance to individual medications due to viral mutations. However, for effective inhibition of a particular virus, a customized approach to combination pharmacotherapy may be essential. Porcine epidemic diarrhea virus (PEDV) is a...

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Main Authors: Yingge Zheng, Yanfei Zhang, Fangying Xiong, Dehua Luo, Yuxiang Wang, Yijia Zhang, Dengguo Wei
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Animal Diseases
Subjects:
Online Access:https://doi.org/10.1186/s44149-025-00157-y
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author Yingge Zheng
Yanfei Zhang
Fangying Xiong
Dehua Luo
Yuxiang Wang
Yijia Zhang
Dengguo Wei
author_facet Yingge Zheng
Yanfei Zhang
Fangying Xiong
Dehua Luo
Yuxiang Wang
Yijia Zhang
Dengguo Wei
author_sort Yingge Zheng
collection DOAJ
description Abstract Cocktail therapy significantly reduces the development of resistance to individual medications due to viral mutations. However, for effective inhibition of a particular virus, a customized approach to combination pharmacotherapy may be essential. Porcine epidemic diarrhea virus (PEDV) is a member of the Coronaviridae family, whose genome consists of a single strand of positive-sense RNA and has evolved into multiple epidemic lineages with no available drugs in clinical practice. In this study, we found that the nucleoside analog gemcitabine decreased the titer of PEDV, with a median effective concentration (EC50) of 3.12 μM, thereby inhibiting viral replication. The natural product baicalein acts by targeting the early entry stage and directly inactivates the virus, with an EC50 of 5.02 μM. A notable synergistic effect was observed with the combination of 1 μM gemcitabine and 1.5 μM baicalein. This study demonstrated that the strategic use of a drug combination targeting both the replication and entry phases of the PEDV lifecycle can effectively inhibit viral proliferation.
format Article
id doaj-art-e6f393aa2ffa4d0cb38a1b5498e36f5d
institution Kabale University
issn 2731-0442
language English
publishDate 2025-02-01
publisher BMC
record_format Article
series Animal Diseases
spelling doaj-art-e6f393aa2ffa4d0cb38a1b5498e36f5d2025-02-09T12:27:15ZengBMCAnimal Diseases2731-04422025-02-01511910.1186/s44149-025-00157-yGemcitabine combined with baicalein exerts antiviral activity against PEDV by inhibiting the entry and replication phasesYingge Zheng0Yanfei Zhang1Fangying Xiong2Dehua Luo3Yuxiang Wang4Yijia Zhang5Dengguo Wei6State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityAbstract Cocktail therapy significantly reduces the development of resistance to individual medications due to viral mutations. However, for effective inhibition of a particular virus, a customized approach to combination pharmacotherapy may be essential. Porcine epidemic diarrhea virus (PEDV) is a member of the Coronaviridae family, whose genome consists of a single strand of positive-sense RNA and has evolved into multiple epidemic lineages with no available drugs in clinical practice. In this study, we found that the nucleoside analog gemcitabine decreased the titer of PEDV, with a median effective concentration (EC50) of 3.12 μM, thereby inhibiting viral replication. The natural product baicalein acts by targeting the early entry stage and directly inactivates the virus, with an EC50 of 5.02 μM. A notable synergistic effect was observed with the combination of 1 μM gemcitabine and 1.5 μM baicalein. This study demonstrated that the strategic use of a drug combination targeting both the replication and entry phases of the PEDV lifecycle can effectively inhibit viral proliferation.https://doi.org/10.1186/s44149-025-00157-yAntivirusGemcitabineBaicaleinSynergistic effectCombination therapy
spellingShingle Yingge Zheng
Yanfei Zhang
Fangying Xiong
Dehua Luo
Yuxiang Wang
Yijia Zhang
Dengguo Wei
Gemcitabine combined with baicalein exerts antiviral activity against PEDV by inhibiting the entry and replication phases
Animal Diseases
Antivirus
Gemcitabine
Baicalein
Synergistic effect
Combination therapy
title Gemcitabine combined with baicalein exerts antiviral activity against PEDV by inhibiting the entry and replication phases
title_full Gemcitabine combined with baicalein exerts antiviral activity against PEDV by inhibiting the entry and replication phases
title_fullStr Gemcitabine combined with baicalein exerts antiviral activity against PEDV by inhibiting the entry and replication phases
title_full_unstemmed Gemcitabine combined with baicalein exerts antiviral activity against PEDV by inhibiting the entry and replication phases
title_short Gemcitabine combined with baicalein exerts antiviral activity against PEDV by inhibiting the entry and replication phases
title_sort gemcitabine combined with baicalein exerts antiviral activity against pedv by inhibiting the entry and replication phases
topic Antivirus
Gemcitabine
Baicalein
Synergistic effect
Combination therapy
url https://doi.org/10.1186/s44149-025-00157-y
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