KUMARI, A. | Search bioRxiv

bioRxiv2026

Antiviral Potential of Lauric Acid against Dengue Virus 2: Evidence from a Luciferase-Based Replicon Assay

Dengue virus (DENV) infection generates a significant health burden throughout the world, and there are no clinically approved antiviral drugs, as of now. The virus also depends on lipid metabolism in the host to conduct effective replication and this makes lipid-directed compounds promising as therapeutic options. We assessed the antiviral effect of lauric acid, a 12-carbon medium-chain fatty acid, against DENV serotype 2 (DV2) in the presence of a stable cell line, DV2-replicon, expressing all the non-structural proteins (NS1-NS5) and a luciferase reporter. Active viral replication in replicon cells was established by morphological examination and immunofluorescence of cells. The MTT assay was used to determine the cytotoxicity of lauric acid revealing the LD50 of 2.52 uM, so higher concentrations were toxic as the effect of the drug is dose-related. The antiviral effect was tested through replicon inhibition (luciferase) assay which showed an incredible inhibition of viral RNA replication with a IC50 of 1.70 uM and this is equivalent to antiviral mycophenolphycic acid. The cytopathic effects, as well as a decrease in the activity of luciferase, proved the presence of viral translation and replication inhibition within the process of the treatment of the lauric acid. These results propose that lauric acid has cytotoxic and antiviral dual effect and can be a possible inhibitor of DENV replication. The toxicity needs to be reduced and future research is necessary to explain its molecular pathway and also to come up with the best delivery methods. IMPORTANCEDengue virus (DENV) remains a significant health challenge to the world since there are no effective antiviral agents. This work will recognize lauric acid as a possible dengue virus replication inhibitor in a model of a DV2 replicon, exhibiting antiviral action that is similar to that of mycophenolic acid. These results support lipid-directed compounds as potential dengue antiviral targets, but more research is needed to minimize toxicity and better understand the molecular mechanism of action.

molecular biology↗

bioRxiv2018

Nitric oxide is important for sensing and survival under hypoxia in Arabidopsis

Nitric oxide (NO) is a free radical molecule that plays an important role in hypoxic stress. We studied the impact of hypoxia-induced NO production on the expression of genes and production of metabolites involved in carbon, oxygen sensing, nitrogen, and antioxidant metabolism using wild type (WT), non-symbiotic haemoglobin-overexpressing (Hb+) and nitrate reductase double mutant (nia1,2) of Arabidopsis. Futher application of NO scavenger cPTIO was used to confirm NO role. We found that imposing hypoxia leads to the increaseof NO and reactive oxygen species (ROS) levels in WT, while the reduced levels of NO and higher levels of ROS were observed in roots of Hb+ and nia1,2 mutant. Expression of the genes encoding oxygen sensing and the enzymes involved in fermentative pathways, their activities and metabolite levels were highly induced in WT suggesting that NO plays a role in the induction of fermentation. Several genes and metabolites involved in the TCA cycle were also induced in WT in comparison to Hb+ and nia mutant line suggesting that NO can accelerate TCA cycle to regenerate reducing equivalents under hypoxia. Interestingly, we found that the genes and metabolites involved in the ascorbate-glutathione cycle were modulated by NO under hypoxia. The alternative oxidasegene (AOX1A) was induced under hypoxia in WTdue to increased levels of NO rather than ROS. Futher, we found that NO improves plant survival. Overall these findings suggest that NO is a major player in plant survival under hypoxia by modulating gene expression and metabolite levels of carbon, nitrogen, oxygen sensing and antioxidant metabolism.\n\nHighlightHypoxia-induced nitric oxide plays a central role in activation of genes and metabolites involved in fermentation, TCA cycle, nitrogen and antioxidant metabolism

plant biology↗