Skip to content
DraconiticResearch
Search Sources API
203,203 studies31 sourcesUpdated 14 min ago
Peer-reviewedCC BY 4.0Antimicrobial Agents and Chemotherapy

Trifluoperazine exhibits broad-spectrum antiviral activity against arboviruses

  • Laxmi Mishra1
  • Manjula Kalia1
  1. 1Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, India
Read full textDOICite

Abstract

The recurrent outbreaks and geographical expansion of mosquito-borne arboviruses pose a significant challenge to public health worldwide. The disease outcome for arboviral infections ranges from acute febrile illness to severe conditions such as encephalitis, hemorrhagic shock, and mortality. Current treatment options for these viruses are limited to supportive care, necessitating an urgent need for a safe and effective broad-spectrum antiviral. In this study, we have identified trifluoperazine (TFP), an FDA-approved antipsychotic, as a potent broad-spectrum antiviral against Japanese encephalitis virus (JEV), Dengue virus (DENV), and Chikungunya virus (CHIKV) infections. The antiviral effect of TFP was also seen in the animal models of JEV and CHIKV with significantly reduced disease severity. Mechanistically, TFP treatment increased the phosphorylation of eIF2a and induced an adaptive ER stress response in diverse cell types. Alleviation of TFP-induced ER stress by chemical chaperone 4PBA abolished the antiviral activity of the drug and rescued virus replication in cells and CHIKV mice model. The robust in vitro and in vivo efficacy of the drug against arboviruses highlights the potential for repurposing TFP as a broad-spectrum antiviral candidate and underscores the importance of ER stress as a therapeutic target.

Related

  1. The Novel Organic Arsenical PZ2 Exhibits Potent Anti-T-ALL Activity via ROS-Dependent Apoptosis and GABARAPL1-Induced Autophagic Cell Death
    Xian Zhang, Zhuping Chen, Yujiao Liu +1
    CancersPeer-reviewedCC BYFull textOncologyEurope PMC
  2. OT-CATH, a conserved antimicrobial peptide in Otariidae species, exhibits potent activity against gram-negative bacteria
    Yixiao Song, Yufeng Ren, Juan Wang +6
    Antimicrobial Agents and ChemotherapyPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyDOAJPMC
  3. NT-A9, a new triazole, exhibits potent antifungal activity against Candida and Cryptococcus species through potent ergosterol biosynthesis inhibition
    Shuo Zhu, Tingjunhong Ni, Lu Gao +5
    Antimicrobial Agents and ChemotherapyPeer-reviewedCC BY 4.0Full textInfectious diseasePMC
  4. Sigma‐1 Receptor‐Targeting Compounds Show Antiviral Activity Across Multiple Coronavirus Models
    Cuiling Zhang, Xingpeng Dong, Jiaying Liu +7
    Journal of medical virologyPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMC
  5. Diethyl fumarate exhibits potent activity against differentially culturable Mycobacterium tuberculosis persisters.
    Amelie J Herbert, Obolbek Turapov, Fraser MacDonald +5
    Frontiers in cellular and infection microbiologyPeer-reviewedCC BYFull textInfectious diseaseEurope PMC

Cite

BibTeXRIS
BibTeX
@article{mishra2026trifluoperazine,
  title = {{Trifluoperazine exhibits broad-spectrum antiviral activity against arboviruses}},
  author = {Laxmi Mishra and Manjula Kalia},
  journal = {Antimicrobial Agents and Chemotherapy},
  year = {2026},
  month = jul,
  doi = {10.1128/aac.00100-26},
  url = {https://doi.org/10.1128/aac.00100-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Trifluoperazine exhibits broad-spectrum antiviral activity against arboviruses
AU  - Laxmi Mishra
AU  - Manjula Kalia
PY  - 2026
DA  - 2026/07/23
JO  - Antimicrobial Agents and Chemotherapy
DO  - 10.1128/aac.00100-26
UR  - https://doi.org/10.1128/aac.00100-26
AB  - The recurrent outbreaks and geographical expansion of mosquito-borne arboviruses pose a significant challenge to public health worldwide. The disease outcome for arboviral infections ranges from acute febrile illness to severe conditions such as encephalitis, hemorrhagic shock, and mortality. Current treatment options for these viruses are limited to supportive care, necessitating an urgent need for a safe and effective broad-spectrum antiviral. In this study, we have identified trifluoperazine (TFP), an FDA-approved antipsychotic, as a potent broad-spectrum antiviral against Japanese encephalitis virus (JEV), Dengue virus (DENV), and Chikungunya virus (CHIKV) infections. The antiviral effect of TFP was also seen in the animal models of JEV and CHIKV with significantly reduced disease severity. Mechanistically, TFP treatment increased the phosphorylation of eIF2a and induced an adaptive ER stress response in diverse cell types. Alleviation of TFP-induced ER stress by chemical chaperone 4PBA abolished the antiviral activity of the drug and rescued virus replication in cells and CHIKV mice model. The robust in vitro and in vivo efficacy of the drug against arboviruses highlights the potential for repurposing TFP as a broad-spectrum antiviral candidate and underscores the importance of ER stress as a therapeutic target.
SN  - 0066-4804
SN  - 1098-6596
ER  -