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Abstract Title:

Drug repurposing of N-acetyl cysteine as antiviral against dengue virus infection.

Abstract Source:

Antiviral Res. 2019 Mar 27. Epub 2019 Mar 27. PMID: 30928439

Abstract Author(s):

Gopinathan Pillai Sreekanth, Jutatip Panaampon, Aroonroong Suttitheptumrong, Aporn Chuncharunee, Jintana Bootkunha, Pa-Thai Yenchitsomanus, Thawornchai Limjindaporn

Article Affiliation:

Gopinathan Pillai Sreekanth

Abstract:

Liver injury is one of the hallmark features of severe dengue virus (DENV) infection since DENV can replicate in the liver and induce hepatocytes to undergo apoptosis. N-acetyl cysteine (NAC), which is a clinically-used drug for treating acetaminophen toxicity, was found to benefit patients with DENV-induced liver injury; however, its mechanism of action remains unclear. Accordingly, our aim was to repurpose NAC in the preclinical studies to investigate its mechanism of action. Time of addition experiments in HepG2 cells elucidated effectiveness of NAC to reduce infectious virion at pre-, during- and post infection. In DENV-infected mice, NAC improved DENV-associated clinical manifestations, including leucopenia and thrombocytopenia, and reduced liver injury and hepatocyte apoptosis. Interestingly, we discovered that NAC significantly reduced DENV production in HepG2 cells and in liver of DENV-infected mice by induction of antiviral responses via interferon signaling. NAC treatment in DENV-infected mice helped to maintain antioxidant enzymes and redox balance in the liver. Therefore, NAC reduces DENV production and oxidative damage to ameliorate DENV-induced liver injury. Taken together, these findings suggest the novel therapeutic potential of NAC in DENV-induced liver injury and recommend evaluating its efficacy and safety in humans with DENV-induced liver injury.

Study Type : Animal Study

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