Tyrosine kinase/phosphatase inhibitors decrease dengue virus production in HepG2 cells

Limjindaporn, Thawornchai; Panaampon, Jutatip; Malakar, Shilu; Noisakran, Sansanee; Yenchitsomanus, Pa‐thai

doi:10.1016/j.bbrc.2017.01.006

Cited by 12 publications

(3 citation statements)

References 33 publications

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“…Previous studies also demonstrated that inhibitors targeting COX-2 and tyrosinase exhibit significant anti-DENV replication [ 43 , 44 ]. Additionally, lucidone exhibits anti-COX-2 and anti-tyrosinase activities in macrophages and melanoma cells, respectively [ 45 , 46 ]. It will be worth investigating whether inhibiting COX-2 or tyrosinase contributes to anti-DENV activity of lucidone in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1

et al. 2018

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Dengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice. Then, the anti-DENV activity of lucidone was confirmed by western blotting and quantitative-reverse-transcription-polymerase chain reaction analysis, with an EC50 value of 25 ± 3 μM. Lucidone significantly induced heme oxygenase-1 (HO-1) production against DENV replication by inhibiting DENV NS2B/3 protease activity to induce the DENV-suppressed antiviral interferon response. The inhibitory effect of lucidone on DENV replication was attenuated by silencing of HO-1 gene expression or blocking HO-1 activity. In addition, lucidone-stimulated nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in transactivation of HO-1 expression for its anti-DENV activity. Taken together, the mechanistic investigations revealed that lucidone exhibits significant anti-DENV activity in in vivo and in vitro by inducing Nrf2-mediated HO-1 expression, leading to blockage of viral protease activity to induce the anti-viral interferon (IFN) response. These results suggest that lucidone is a promising candidate for drug development.

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Section: Discussionmentioning

confidence: 99%

Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1

et al. 2018

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“…On the other hand, euparin derivatives showed protein tyrosine phosphatase 1B (PTP1B) inhibition in vitro [ 27 ]. It has been demonstrated that inhibitors of PTP1B can decrease DENV multiplication in HepG2 cells [ 28 ]. We can hypothesize that euparin could produce similar effects on DENV-2, and consequently, additional efforts should be invested in the elucidation of its molecular mechanism and the anti-DENV potential of this molecule.…”

Section: Discussionmentioning

confidence: 99%

Plant Extracts and Phytochemicals from the Asteraceae Family with Antiviral Properties

Borgo,

Wagner,

Laurella

et al. 2024

Molecules

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Asteraceae (Compositae), commonly known as the sunflower family, is one of the largest plant families in the world and includes several species with pharmacological properties. In the search for new antiviral candidates, an in vitro screening against dengue virus (DENV) was performed on a series of dichloromethane and methanolic extracts prepared from six Asteraceae species, including Acmella bellidioides, Campuloclinium macrocephalum, Grindelia pulchella, Grindelia chiloensis, Helenium radiatum, and Viguiera tuberosa, along with pure phytochemicals isolated from Asteraceae: mikanolide (1), eupatoriopicrin (2), eupahakonenin B (3), minimolide (4), estafietin (5), 2-oxo-8-deoxyligustrin (6), santhemoidin C (7), euparin (8), jaceidin (9), nepetin (10), jaceosidin (11), eryodictiol (12), eupatorin (13), and 5-demethylsinensetin (14). Results showed that the dichloromethane extracts of C. macrocephalum and H. radiatum and the methanolic extracts prepared from C. macrocephalum and G. pulchella were highly active and selective against DENV-2, affording EC50 values of 0.11, 0.15, 1.80, and 3.85 µg/mL, respectively, and SIs of 171.0, 18.8, >17.36, and 64.9, respectively. From the pool of phytochemicals tested, compounds 6, 7, and 8 stand out as the most active (EC50 = 3.7, 3.1, and 6.8 µM, respectively; SI = 5.9, 6.7, and >73.4, respectively). These results demonstrate that Asteraceae species and their chemical constituents represent valuable sources of new antiviral molecules.

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“…The EGFR TKI gefitinib was found to decrease respiratory viral burden in C57Bl/6 mice infected with IAV in both prophylactic and therapeutic models, a mechanism dependent on higher levels of IFN‐λ produced by respiratory epithelial cells in gefitinib‐treated animals . EGFR blockade has also been found to inhibit the pathogenesis of poxvirus, dengue virus, and viral hemorrhagic fevers in in vitro studies. Due to its importance in maintaining cellular homeostasis, it is unsurprising that many viruses have evolved mechanisms to co‐opt the EGFR signaling pathway for their gain.…”

Section: The Use Of Targeted Therapies Outside Of Advanced Cancermentioning

confidence: 99%

Targeted Therapies: Immunologic Effects and Potential Applications Outside of Cancer

Kersh

Chang

et al. 2017

The Journal of Clinical Pharma

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Two pharmacologic approaches that are currently at the forefront of treating advanced cancer are those that center on disrupting critical growth/survival signaling pathways within tumor cells (commonly referred to as "targeted therapies") and those that center on enhancing the capacity of a patient's immune system to mount an antitumor response (immunotherapy). Maximizing responses to both of these approaches requires an understanding of the oncogenic events present in a given patient's tumor and the nature of the tumor-immune microenvironment. Although these 2 modalities were developed and initially used independently, combination regimens are now being tested in clinical trials, underscoring the need to understand how targeted therapies influence immunologic events. Translational studies and preclinical models have demonstrated that targeted therapies can influence immune cell trafficking, the production of and response to chemokines and cytokines, antigen presentation, and other processes relevant to antitumor immunity and immune homeostasis. Moreover, because these and other effects of targeted therapies occur in nonmalignant cells, targeted therapies are being evaluated for use in applications outside of oncology.

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Tyrosine kinase/phosphatase inhibitors decrease dengue virus production in HepG2 cells

Cited by 12 publications

References 33 publications

Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1

Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1

Plant Extracts and Phytochemicals from the Asteraceae Family with Antiviral Properties

Targeted Therapies: Immunologic Effects and Potential Applications Outside of Cancer

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