Abstract
Dengue virus (DENV) caused millions of infections around the world annually. Co-infection with different serotypes of DENV is associated with dengue hemorrhagic shock syndrome, leading to an estimate of 50% death rate. No approved therapies are currently available for the treatment of DENV infection. Hence, novel anti-DENV agents are urgently needed for medical therapy. Here we demonstrated that a natural product (2 R,4 R)-1,2,4-trihydroxyheptadec-16-yne (THHY), extracted from avocado (Persea americana) fruit, can inhibit DENV-2 replication in a concentration-dependent manner and efficiently suppresses replication of all DENV serotypes (1–4). We further reveal that the NF-κB-mediated interferon antiviral response contributes to the inhibitory effect of THHY on DENV replication. Using a DENV-infected ICR suckling mouse model, we found that THHY treatment caused an increased survival rate among mice infected with DENV. Collectively, these findings support THHY as a potential agent to control DENV infection.
Highlights
The clinical manifestations of dengue fever[9]
IκB kinase (IKK) activation initiates inhibitors of κBα (IκBα) phosphorylation and the degradation of IκBα, which leads to the translocation of nuclear factor-κB (NF-κB) into the nucleus to trigger IFN regulatory factor (IRF) and IFN-I expression and secretion
Based on the primary anti-Dengue virus (DENV) screening of several constituents extracted from avocado using a cell-based DENV infectious system, we identified a component (2 R,4 R)-1,2,4-trihydroxyheptadec-16-yne (Fig. 1A), named THHY, with significant anti-DENV activity
Summary
IFN-α secretion was increased by THHY treatment (Fig. 3C) These results revealed that THHY inhibits DENV replication via up-regulation of NF-κB-mediated antiviral IFN-α expression. The results of RT-qPCR revealed that the levels of IFN-stimulated antiviral gene expression were increase by THHY treatment in DENV-2-infected cells (Fig. 4C–F). These results support that THHY inhibits DENV-2 replication via upregulation of IFN-α and STAT1/2-triggered antiviral responses. In the study of inhibitory properties against DENV of THHY, we clearly verified that THHY suppressed DENV replication through up-regulation of NF-κB-mediated antiviral IFN responses (Figs 2–4), which is consistent with previous reports that stimulation of IFN-induced antiviral pathway is a promising strategy against DENV infection[20,21]. THHY protected ICR suckling mice against death by DENV infection in vivo, allowing avocado fruit to serve as a potential dietary resource to develop a supplement for the treatment DENV infection and DENV-related diseases
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