Evaluation of the Antiviral Activity of Monomeric, Dimeric, and Oligomeric Flavonoids against Chikungunya and Mayaro Viruses

Identification of 4-Amino-7-chloroquinoline Derivative with In Vitro Activity Against Chikungunya Virus

Among the tested compounds, derivative 6 demonstrated the most pronounced anti-CHIKV activity, with a low micromolar effective concentration and moderate selectivity index, and was identified as a potential lead candidate for further development against CHIKV.

IN SILICO EVALUATION OF ANTIVIRAL POTENTIAL OF EMBLICA OFFICINALIS PHYTOCONSTITUENTS TARGETING CHIKUNGUNYA VIRUS NSP3 PROTEIN

Findings suggest that bioactive compounds from E. officinalis may serve as promising candidates for the development of anti-CHIKV therapeutics, however, further experimental validation is required to confirm their efficacy and safety.

Eugenol‐Derived Piperazine Mannich Bases as Selective Inhibitors of Mayaro Virus: In Vitro Antiviral Evaluation and Mechanistic Insights

Arboviruses represent an ongoing global health challenge, particularly in tropical regions where diseases caused by Chikungunya virus (CHIKV) and Mayaro virus (MAYV) continue to emerge. Given the absence of licensed antiviral therapies, the identification of effective small molecules remains critical. This study evaluated sixteen eugenol‐ and dihydroeugenol‐derived piperazine Mannich bases for antiviral activity against CHIKV, MAYV, and Zika virus (ZIKV) in Vero cells. Cytotoxicity was assessed using the MTT assay, and antiviral activity was quantified through median effective concentration (EC50) and selectivity index (SI) values. Time‐dependent cytopathic effect inhibition, plaque reduction assays, virucidal assays and docking were performed to characterize the mechanism of action. Three compounds (D3, D7, and E7) exhibited selective antiviral activity. Notably, compound D7 demonstrated low‐micromolar anti‐MAYV inhibition (EC50 = 14.43 μM; SI > 16.6), surpassing ribavirin by more than thirty‐fold in relative potency. Time‐dependent assays revealed progressive viral titer reductions of up to 3 log10 PFU/mL over 48 h. Virucidal assays confirmed that D7 does not directly inactivate viral particles. These findings identify D7 as a promising antiviral lead compound and provide a foundation for further mechanistic, optimization, and in vivo studies aimed at developing anti‐alphavirus therapeutics.

Antiviral Activity of Synthetic Bis-Naphthoquinone (H-5) Against Chikungunya Virus Replication

Anticandidal, molecular docking, antioxidant, and cytotoxic effects of the essential oil of Vitex gardneriana Schauer.

Vitex gardneriana Schauer, known as "Jaramataia", is widely used in folk medicine for its anti-inflammatory and analgesic properties. This study aimed to determine the chemical composition and evaluate the antifungal, antioxidant, and cytotoxic effects of the essential oil (EO) from its leaves. The EO was obtained via hydrodistillation and analyzed by GC-FID, identifying 16 components, with trans-calamenene (25.31%), 6,9-guaiadiene (18.33%), and caryophyllene oxide (15.14%) as major compounds. Antifungal activity was assessed by broth microdilution, showing a MIC of 5 mg/mL for all strains. A synergistic effect was observed when combined with amphotericin B, reducing the EO's inhibitory concentration by over 30-fold. Antioxidant activity (DPPH method) showed an IC50 of 85.86 mg/mL, while hemolytic assays on human erythrocytes showed an IC50 of 20 mg/mL. Molecular docking revealed a stronger affinity of EO compounds to Sap5 (-7.3 kcal/mol) than Als3 (-6.2 kcal/mol), with some ligands (e.g., 1-epi-cubenol, caryophyllene oxide) binding to different regions than amphotericin B. These findings suggest that V. gardneriana EO has moderate antifungal activity. However, it shows promising potential when combined with conventional antifungal agents and supports future research toward the development of therapeutic formulations.

Pyridin-3-carbohydrazide strongly impairs Mayaro and Chikungunya virus replication in vitro

Alphaviruses, including Mayaro virus (MAYV) and Chikungunya virus (CHIKV), pose a growing public health threat, with increasing reports worldwide and no licensed antiviral treatments available. This study evaluated the antiviral activity of pyridine-3-carbohydrazide (P-3-C) against MAYV (strains BeAr and TRVL) and CHIKV (strain La Reunion, LR). Vero E6 or U-2OS cells were infected and treated with P-3-C for 24 h, and cell viability and replication levels were assessed. The 50% cytotoxic concentration (CC50), 50% effective concentration (EC50), and selective index (SI) were calculated. P-3-C showed concentration-dependent activity, strongly inhibiting post-entry stages of MAYV BeAr replication. Treatment reduced intracellular viral RNA levels by 2 log10 compared with controls and effectively decreased viral RNA release. P-3-C also inhibited MAYV TRVL (SI > 29.4) and CHIKV LR (SI > 48.8) in Vero E6 cells and retained selectivity in U-2OS cells (SI = 3.9 and 6.4, respectively). In a CHIKV U-2OS subgenomic replicon, an SI of 4.1 was found. Additionally, Fluorometric FRET-Based and MicroScale Thermophoresis (MST) assays indicated that P-3-C inhibited the nsP2 protease activity (IC50 = 12 µM ± 2) and exhibited binding affinity for nsP4 polymerase (Kd = 54 µM ± 1) from CHIKV, thereby suggesting that these non-structural proteins are potential molecular targets. Molecular docking positioned P-3-C within the catalytic pockets of nsP2 and nsP4 of both viruses. Overall, the data suggest that P-3-C exhibits a potential multitarget mechanism of action and highlight its antiviral activity against different alphavirus strains; however, this efficacy could be dependent on the cell line used.