Antiviral Activity of Compound L3 against Dengue and Zika Viruses In Vitro and In Vivo

Chuang, Fu-Kai; Liao, Ching‐Len; Hu, Ming‐Kuan; Chiu, Yi‐Lin; Lee, An‐Rong; Huang, Shih‐Ming; Chiu, Yu‐Lung; Tsai, Pei-Ling; Su, Bo-Cyuan; Chang, Tsung-Hsien; Lin, Cheng Wen; Shih, Chun Kuang; Yen, Li-Chen

doi:10.3390/ijms21114050

Cited by 11 publications

(6 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vero cells were maintained at 37 • C with 5% CO 2 in DMEM (Gibco) supplemented with 10% heat-inactivated FBS (Gibco). All cell culture efficacy and toxicity experiments were conducted with HEK-293 cells, an interferon competent human cell line that supports flavivirus replication and is often used to evaluate potency and toxicity of potential antivirals [39][40][41][42][43][44][45].…”

Section: Cellsmentioning

confidence: 99%

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

Scroggs

Andrade

Ramesh

et al. 2020

Viruses

View full text Add to dashboard Cite

Repurposing FDA-approved compounds could provide the fastest route to alleviate the burden of disease caused by flaviviruses. In this study, three fluoroquinolones, enoxacin, difloxacin and ciprofloxacin, curtailed replication of flaviviruses Zika (ZIKV), dengue (DENV), Langat (LGTV) and Modoc (MODV) in HEK-293 cells at low micromolar concentrations. Time-of-addition assays suggested that enoxacin suppressed ZIKV replication at an intermediate step in the virus life cycle, whereas ciprofloxacin and difloxacin had a wider window of efficacy. A129 mice infected with 1 × 105 plaque-forming units (pfu) ZIKV FSS13025 (n = 20) or phosphate buffered saline (PBS) (n = 11) on day 0 and treated with enoxacin at 10 mg/kg or 15 mg/kg or diluent orally twice daily on days 1–5 did not differ in weight change or virus titer in serum or brain. However, mice treated with enoxacin showed a significant, five-fold decrease in ZIKV titer in testes relative to controls. Mice infected with 1 × 102 pfu ZIKV (n = 13) or PBS (n = 13) on day 0 and treated with 15 mg/kg oral enoxacin or diluent twice daily pre-treatment and days 1–5 post-treatment also did not differ in weight and viral load in the serum, brain, and liver, but mice treated with enoxacin showed a significant, 2.5-fold decrease in ZIKV titer in testes relative to controls. ZIKV can be sexually transmitted, so reduction of titer in the testes by enoxacin should be further investigated.

show abstract

Section: Cellsmentioning

confidence: 99%

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

Scroggs

Andrade

Ramesh

et al. 2020

Viruses

View full text Add to dashboard Cite

show abstract

“…Previous studies gave evidence that the EGFR pathway plays a role in producing various viruses, such as DENV, ZIKV, etc (Ueki et al, 2013 ; Lin et al, 2019 ; Chuang et al, 2020 ). To explore whether EGFR is involved in the JEV infection process, cells were pretreated with AG1478 or gefitinib in different concentrations.…”

Section: Resultsmentioning

confidence: 99%

EGFR Activation Impairs Antiviral Activity of Interferon Signaling in Brain Microvascular Endothelial Cells During Japanese Encephalitis Virus Infection

et al. 2022

View full text Add to dashboard Cite

The establishment of Japanese encephalitis virus (JEV) infection in brain microvascular endothelial cells (BMECs) is thought to be a critical step to induce viral encephalitis with compromised blood–brain barrier (BBB), and the mechanisms involved in this process are not completely understood. In this study, we found that epidermal growth factor receptor (EGFR) is related to JEV escape from interferon-related host innate immunity based on a STRING analysis of JEV-infected primary human brain microvascular endothelial cells (hBMECs) and mouse brain. At the early phase of the infection processes, JEV induced the phosphorylation of EGFR. In JEV-infected hBMECs, a rapid internalization of EGFR that co-localizes with the endosomal marker EEA1 occurred. Using specific inhibitors to block EGFR, reduced production of viral particles was observed. Similar results were also found in an EGFR-KO hBMEC cell line. Even though the process of viral infection in attachment and entry was not noticeably influenced, the induction of IFNs in EGFR-KO hBMECs was significantly increased, which may account for the decreased viral production. Further investigation demonstrated that EGFR downstream cascade ERK, but not STAT3, was involved in the antiviral effect of IFNs, and a lowered viral yield was observed by utilizing the specific inhibitor of ERK. Taken together, the results revealed that JEV induces EGFR activation, leading to a suppression of interferon signaling and promotion of viral replication, which could provide a potential target for future therapies for the JEV infection.

show abstract

“…A range of these drugs is already used in oncology, and their repurpose for neglected diseases would be advantageous as it would reduce the time needed to develop therapies for them de novo [ 113 ]. In recent years, several studies have been published on anti-GFR tyrosine kinase inhibitors (TKIs) in dengue, such as dasatinib [ 114 ], sunitinib/erlotinib [ 115 ], gefitinib [ 116 ], brivanib [ 117 ], afatinib-derivative (L3) [ 118 ], sunitinib/anti-TNF antibody [ 119 ], and TGF-β receptor 1 and 2 inhibitors (GW788388) [ 93 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Growth Factors in the Pathogenesis of Dengue: A Scoping Review

2022

View full text Add to dashboard Cite

Growth factors (GFs) have a role in tissue repair and in the modulation of the expression of inflammatory cells in damage caused by pathogens. This study aims to systematize the evidence on the role of GFs in the pathogenesis of dengue. This scoping review considered all published peer-reviewed studies in the MEDLINE and Embase databases. Ultimately, 58 studies that analyzed GFs in dengue patients, published between 1998 and 2021, were included. DENV-2 infection and secondary infection were more frequent in the patients studied. ELISA and multiplex immunoassay (Luminex) were the most used measurement techniques. Increased levels of vascular endothelial growth factor, granulocyte–macrophage colony-stimulating factor, granulocyte colony-stimulating factor, transforming growth factor beta, and hepatocyte growth factor as well as reduced levels of platelet-derived growth factor and epidermal growth factor were observed in severe dengue in most studies. Vascular endothelial growth factor and hepatocyte growth factor were identified as biomarkers of severity. In addition, there is evidence that the dengue virus can use the growth factor pathway to facilitate its entry into the cell and promote its viral replication. The use of tyrosine kinase inhibitors is an alternative treatment for dengue that is being studied.

show abstract

Antiviral Activity of Compound L3 against Dengue and Zika Viruses In Vitro and In Vivo

Cited by 11 publications

References 36 publications

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

EGFR Activation Impairs Antiviral Activity of Interferon Signaling in Brain Microvascular Endothelial Cells During Japanese Encephalitis Virus Infection

The Role of Growth Factors in the Pathogenesis of Dengue: A Scoping Review

Contact Info

Product

Resources

About