Zika virus (ZIKV) infection is a serious public health concern. ZIKV infection has been associated with increased occurrences of microcephaly among newborns and incidences of Guillain-Barré syndrome among adults. No specific therapeutics or vaccines are currently available to treat and protect against ZIKV infection. Here, a plant-secreted phytoalexin, resveratrol (RES), was investigated for its ability to inhibit ZIKV replication in vitro. Several RES treatment regimens were used. The ZIKV titers of mock- and RES-treated infected cell cultures were determined using the focus-forming assay and the Zika mRNA copy number as determined using qRT-PCR. Our results suggested that RES treatment reduced ZIKV titers in a dose-dependent manner. A reduction of >90% of virus titer and ZIKV mRNA copy number was achieved when infected cells were treated with 80 µM of RES post-infection. Pre-incubation of the virus with 80 µM RES showed >30% reduction in ZIKV titers and ZIKV mRNA copy number, implying potential direct virucidal effects of RES against the virus. The RES treatment reduced >70% virus titer in the anti-adsorption assay, suggesting the possibility that RES also interferes with ZIKV binding. However, there was no significant decrease in ZIKV titer when a short-period of RES treatment was applied to cells before ZIKV infection (pre-infection) and after the virus bound to the cells (virus internalization inhibition), implying that RES acts through its continuous presence in the cell cultures after virus infection. Overall, our results suggested that RES exhibited direct virucidal activity against ZIKV and possessed anti-ZIKV replication properties, highlighting the need for further exploration of RES as a potential antiviral molecule against ZIKV infection.

Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection. This migration is inhibited by RESV treatment and is mediated by induction of Sirt1 which leads to the retention of HMGB1 in the nucleus and consequently helps in the increased production of interferon-stimulated genes (ISGs). Nuclear HMGB1 was found to bind to the promoter region of the ISG and positively regulated the expression of ISG. The enhanced transcription of ISGs by nuclear HMGB1 thus contributes to the antiviral activity of RESV against DENV. To the best of our knowledge, this is the first report to demonstrate that RESV antagonizes DENV replication and that nuclear HMGB1 plays a role in regulating ISG production.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global healthcare systems and spurred extensive research efforts over the past three years. One critical aspect of the disease is the intricate interplay between the virus and the host immune response, particularly the role of inflammatory gene expression in severe COVID-19. While numerous previous studies have explored the role of genetic polymorphisms in COVID-19, research specifically focusing on inflammatory genes and their associations with disease severity remains limited. This review explores the relationship between severe COVID-19 outcomes and genetic polymorphisms within key inflammatory genes. By investigating the impact of genetic variations on immune responses, which include cytokine production and downstream signalling pathways, we aim to provide a comprehensive overview of how genetic polymorphisms contribute to the variability in disease presentation. Through an in-depth analysis of existing literature, we shed light on potential therapeutic targets and personalized approaches that may enhance our understanding of disease pathogenesis and treatment strategies.

Neonatal microcephaly and adult Guillain–Barré syndrome are severe complications of Zika virus (ZIKV) infection. The robustly induced inflammatory cytokine expressions in ZIKV-infected patients may constitute a hallmark for severe disease. In the present study, the potential role of high mobility group box 1 protein (HMGB1) in ZIKV infection was investigated. HMGB1 protein expression was determined by the enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. HMGB1’s role in ZIKV infection was also explored using treatment with dexamethasone, an immunomodulatory drug, and HMGB1-knockdown (shHMGB1) Huh7 cells. Results showed that the Huh7 cells were highly susceptible to ZIKV infection. The infection was found to induce HMGB1 nuclear-to-cytoplasmic translocation, resulting in a > 99% increase in the cytosolic HMGB1 expression at 72-h post-infection (h.p.i). The extracellular HMGB1 level was elevated in a time- and multiplicity of infection (MOI)-dependent manner. Treatment of the ZIKV-infected cells with dexamethasone (150 µM) reduced HMGB1 extracellular release in a dose-dependent manner, with a maximum reduction of 71 ± 5.84% (P < 0.01). The treatment also reduced virus titers by over 83 ± 0.50% (P < 0.01). The antiviral effects, however, were not observed in the dexamethasone-treated shHMGB1 cells. These results suggest that translocation of HMGB1 occurred during ZIKV infection and inhibition of the translocation by dexamethasone coincided with a reduction in ZIKV replication. These findings highlight the potential of targeting the localization of HMGB1 in affecting ZIKV infection.