Currently, there are no therapies to prevent severe dengue disease. Essential oils (EOs) can serve as primary sources for research and the discovery of phytomedicines for alternative therapy. Fourteen EOs samples were obtained by distillation from six plants used in Colombian folk medicine. GC/MS analysis identified 125 terpenes. Cytopathic effect (CPE) reduction assays revealed differences in antiviral activity. EOs of Lippia alba, citral chemotype and carvone-rich fraction; Lippia origanoides, phellandrene chemotype; and Turnera diffusa, exhibited strong antiviral activity (IC₅₀: 29 to 82 µg/mL; SI: 5.5 to 14.3). EOs of Piper aduncum, Ocimum basilicum, and L. origanoides, carvacrol, and thymol chemotypes, exhibited weak antiviral activity (32 to 53% DENV-CPE reduction at 100 µg/mL; SI > 5.0). Cluster and one-way ANOVA analyses suggest that the strong antiviral activity of EOs could be attributed to increased amounts of non-phenolic oxygenated monoterpenes and sesquiterpene hydrocarbons. Docking analyses (AutoDock Vina) predicted binding affinity between the DENV-2 E protein and terpenes: twenty sesquiterpene hydrocarbons (−8.73 to −6.91 kcal/mol), eight oxygenated monoterpenes (−7.52 to −6.98 kcal/mol), and seven monoterpene hydrocarbons (−7.60 to −6.99 kcal/mol). This study reports for the first time differences in the antiviral activity of EOs against DENV, corresponding to their composition of monoterpenes and sesquiterpenes.

The large-scale use of alcohol (OH)-based disinfectants to control pathogenic viruses is of great concern because of their side effects on humans and harmful impact on the environment. There is an urgent need to develop safe and environmentally friendly disinfectants. Essential oils (EOs) are generally recognized as safe (GRAS) by the FDA, and many exhibit strong antiviral efficacy against pathogenic human enveloped viruses. The present study investigated the virucidal disinfectant activity of solutions containing EO and OH against DENV-2 and CHIKV, which were used as surrogate viruses for human pathogenic enveloped viruses. The quantitative suspension test was used. A solution containing 12% EO + 10% OH reduced > 4.0 log10 TCID₅₀ (100% reduction) of both viruses within 1 min of exposure. In addition, solutions containing 12% EO and 3% EO without OH reduced > 4.0 log10 TCID₅₀ of both viruses after 10 min and 30 min of exposure, respectively. The binding affinities of 42 EO compounds and viral envelope proteins were investigated through docking analyses. Sesquiterpene showed the highest binding affinities (from −6.7 to −8.0 kcal/mol) with DENV-2 E and CHIKV E1-E2-E3 proteins. The data provide a first step toward defining the potential of EOs as disinfectants.

The continuous emergence of SARS-CoV-2 variants underscores the need for novel antiviral candidates. Hypericin (HY), a compound derived from Hypericum perforatum, exhibited potent in vitro activity against SARS-CoV-2 in Vero E6 cells, with low cytotoxicity (CC₅₀ > 200 nM). HY showed no significant activity against Influenza A (H1N1) or dengue virus serotype 2, supporting its selective action. Antiviral effects were most evident when HY was administered post-infection, in a concentration-dependent manner, while cellular pretreatment or viral pre-incubation produced limited effects. Notably, HY also displayed virucidal activity, significantly reducing viral titers at 4 °C, 22 °C, and 37 °C. Combination treatments with remdesivir or nirmatrelvir enhanced antiviral efficacy by 50–70% relative to monotherapy, depending on compound concentration. Molecular simulations revealed stable interactions with conserved residues in RdRp and 3CLpro, suggesting a low risk of resistance. Together, these findings highlight the potential of HY as a selective antiviral and virucidal agent against SARS-CoV-2, particularly in combination regimens.

The lack of effective conventional therapies against dengue has created an interest in herbal preparations as alternative therapies. In the present study, in vitroeffects of Cordia curassavicaessential oil (EO) on both dengue virus replication and cytokine production were examined. Predictions ofmolecular interactions between EO compounds and virus and cell proteins were performed with AutoDock Vina. The EO inhibited replication of dengue virus serotypes at IC50< 30 μg/mL, and it reduced 87% TNF-α, 67% IL-8 and 46% IFN-α in LPS-stimulated PBMCs.The main EO compounds were trans-β-caryophyllene (21.4%), germacrene D (17.8%), α-copaene (16.5%), trans-β-guaiene (8.2%), and α-pinene (6.0%). The first two compounds, δ-cadinene, α-muurolene, α-cubebene and β-burbonene were coupled to proteins involved in the TLR-4 cytokine effector pathway. 3,7-Guaiadiene was coupled to the viral E and C proteins. This study demonstrates the potential of C. curassavicaEO as a starting point for discovering novel therapeutic for dengue.

The persistent global threat posed by emerging and re-emerging RNA viruses, including SARS-CoV-2, influenza A(H1N1)pdm09, DENV-2, and CHIKV, highlights the critical need for novel and broad-spectrum antiviral agents. Building upon the established antiviral activity of the quinoline scaffold, this study employed a molecular hybridization strategy to design and synthesize a novel series of 1,2,3-triazole–quinoline derivatives (compounds 4a–4h). This approach strategically fused the bioactive quinoline nucleus with the pharmaceutically favorable 1,2,3-triazole ring. The new compounds were synthesized efficiently in three steps with moderate-to-high yields, and their structures were subsequently determined. Their inhibitory capacities against the four viruses and cytotoxicity across relevant cell lines were evaluated in vitro. The initial screening demonstrated that compounds 4a–4h possessed broad-spectrum antiviral activity, showing high inhibition percentages at 10 µM against SARS-CoV-2, DENV-2, and CHIKV. Notably, compounds 4c and 4e, substituted with methoxy and ethyl groups, respectively, displayed exceptional potency and safety against SARS-CoV-2, yielding high selectivity indices (SI: 1896.5 and 1265.8, respectively). Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) and molecular docking calculations suggested favorable drug-likeness profiles, including improved lipophilicity and non-P-glycoprotein substrate feasibility. The findings validate the molecular hybridization strategy, establishing this new class of compounds as promising, multi-target antiviral prototypes for further preclinical exploration against prevalent viral pathogens.