Analysis of fluoro based pyrazole analogues as a potential therapeutics candidate against Japanese encephalitis virus infection

Gupta, Anjali; Gawandi, Sinthiya J.; Vandna, Vandna; Yadav, Inderjeet; Mohan, Hari; Desai, Vidya G.; Kumar, Sachin

doi:10.1016/j.virusres.2022.198955

Cited by 8 publications

(4 citation statements)

References 61 publications

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“…Like SOD1, there are many other anti-oxidative proteins that are manipulated differentially by most of the flaviviridae members. JEV is reported to decrease ROS scavenging via downregulation of proteins like DJ-1 as well as Nrf2-mediated expression of SQSTM1 and thioredoxin (37, 55). Thus, there is a significant role of oxidative stress-induced ROS in shaping the cellular milieu to favor JEV propagation.…”

Section: Discussionmentioning

confidence: 99%

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Alpha-synuclein expression in neuron modulates the Japanese encephalitis virus infection

Gupta,

Mohapatra,

Kaur

et al. 2023

Preprint

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Japanese encephalitis virus (JEV) stands as a prominent vector-borne zoonotic pathogen, displaying neurotropism and eliciting Parkinson’s disease (PD)-like symptoms among most symptomatic survivors. A characteristic feature of PD is aggregation of mutated α-synuclein (α-syn) that damages the dopaminergic neurons. Considering this link between JEV-induced PD-like symptoms and α-syn pathogenesis, we explored the role of α-syn in JEV infectivity in neuronal cells. Our investigation revealed significant increase in endogenous α-syn expression in JEV-infected cells. Additionally, treatment with exogenous α-syn (Exoα-syn) led to a substantial reduction in JEV replication, suggesting its anti-JEV effect. Furthermore, Exoα-syn treatment led to the upregulation of superoxide dismutase 1 (SOD1) and reduction in reactive oxygen species (ROS). The results were validated by endogenous α-syn-silencing, that decreased SOD1 level and raised ROS level in neuronal cells. Similarly, the SOD1 inhibition via LCS-1 also intensified ROS and JEV infection. Overall, our results suggest that α-syn exerts an anti-JEV effect by regulating protein involved in oxidative stress inside neuronal cells. This study contributes valuable insights into the interplay between α-syn expression and JEV infectivity, shedding light on avenues to further investigate the potential role of α-syn in JEV pathogenesis.ImportanceJapanese encephalitis virus (JEV) poses significant threat particularly to children. Despite extensive research efforts, the development of effective treatments against JEV has been impeded. One of the major setbacks is a lack of comprehensive understanding of neurotropism. The study focuses on alpha synuclein (α-syn), a neuronal protein, and aims to determine its role in JEV pathogenesis. Present study reveals that host cell upregulates α-syn in response of JEV infection. α-syn restrains JEV propagation by modulating superoxide dismutase 1 (SOD1) expression which further blocks JEV-induced ROS generation. Endogenous α-syn silencing led to decrease in SOD1 expression and increased viral titer. α-syn plays crucial role in counteracting oxidative stress through SOD1, which is essential for limiting JEV replication. This study provides broader implications for antiviral strategies and its possible role in neurodegenerative diseases; however, there is still much to explore, particularly regarding its aggregation kinetics in JEV infection.

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Section: Discussionmentioning

confidence: 99%

“…The relative quantification was done using ImageJ software. For JEV particle quantification, plaque assay was performed in BHK-21 cells using standard protocol (37).…”

Section: Time-course Analysis Of α-Syn Expressionmentioning

confidence: 99%

Alpha-synuclein expression in neuron modulates the Japanese encephalitis virus infection

Gupta,

Mohapatra,

Kaur

et al. 2023

Preprint

Self Cite

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“…Aloe emodin and chrysophanol, the methanol extracts of Rheum palmatum , were demonstrated to inhibit JEV replication by activating gamma-activated sequence (GAS)-driven genes to indirectly initiate IFN-γ -triggered host innate immune responses against JEV infection in vitro [ 39 ]. Another in vitro study demonstrated that aloe emodin could inhibit JEV replication by activating the IFN-stimulated response element (ISRE) and GAS-driven cis-reporting systems associated with the activation of type I and II IFN responses, and the up-regulation of the expression of IFN-stimulated genes [ 120 ].…”

Section: Antivirals Against Jev Infectionmentioning

confidence: 99%

Recent Advances in Antivirals for Japanese Encephalitis Virus

Zhu

Chen

Lurong

et al. 2023

Viruses

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Culex mosquitoes are the primary vectors of the Japanese encephalitis virus (JEV). Since its discovery in 1935, Japanese encephalitis (JE), caused by JEV, has posed a significant threat to human health. Despite the widespread implementation of several JEV vaccines, the transmission chain of JEV in the natural ecosystem has not changed, and the vector of transmission cannot be eradicated. Therefore, JEV is still the focus of attention for flaviviruses. At present, there is no clinically specific drug for JE treatment. JEV infection is a complex interaction between the virus and the host cell, which is the focus of drug design and development. An overview of antivirals that target JEV elements and host factors is presented in this review. In addition, drugs that balance antiviral effects and host protection by regulating innate immunity, inflammation, apoptosis, or necrosis are reviewed to treat JE effectively.

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“…The spleen is the main immune organ, and it plays important roles in filtering blood-borne pathogens and antigens to protect the host against various infectious diseases and pathogen infections [ 29 , 30 , 31 ]. Herein, the spleen is regarded as the ideal organ model for exploring host resistance and susceptibility to pathogenic challenges.…”

Section: Introductionmentioning

confidence: 99%

Change in Long Non-Coding RNA Expression Profile Related to the Antagonistic Effect of Clostridium perfringens Type C on Piglet Spleen

Yan

Wang

Yang

et al. 2023

CIMB

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LncRNAs play important roles in resisting bacterial infection via host immune and inflammation responses. Clostridium perfringens (C. perfringens) type C is one of the main bacteria causing piglet diarrhea diseases, leading to major economic losses in the pig industry worldwide. In our previous studies, piglets resistant (SR) and susceptible (SS) to C. perfringens type C were identified based on differences in host immune capacity and total diarrhea scores. In this paper, the RNA-Seq data of the spleen were comprehensively reanalyzed to investigate antagonistic lncRNAs. Thus, 14 lncRNAs and 89 mRNAs were differentially expressed (DE) between the SR and SS groups compared to the control (SC) group. GO term enrichment, KEGG pathway enrichment and lncRNA-mRNA interactions were analyzed to identify four key lncRNA targeted genes via MAPK and NF-κB pathways to regulate cytokine genes (such as TNF-α and IL-6) against C. perfringens type C infection. The RT-qPCR results for six selected DE lncRNAs and mRNAs are consistent with the RNA-Seq data. This study analyzed the expression profiling of lncRNAs in the spleen of antagonistic and sensitive piglets and found four key lncRNAs against C. perfringens type C infection. The identification of antagonistic lncRNAs can facilitate investigations into the molecular mechanisms underlying resistance to diarrhea in piglets.

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Analysis of fluoro based pyrazole analogues as a potential therapeutics candidate against Japanese encephalitis virus infection

Cited by 8 publications

References 61 publications

Alpha-synuclein expression in neuron modulates the Japanese encephalitis virus infection

Alpha-synuclein expression in neuron modulates the Japanese encephalitis virus infection

Recent Advances in Antivirals for Japanese Encephalitis Virus

Change in Long Non-Coding RNA Expression Profile Related to the Antagonistic Effect of Clostridium perfringens Type C on Piglet Spleen

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