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Evaluation of Antiviral Activity of Cyclic Ketones against Mayaro Virus
Luciana S Fernandes1, Milene L da Silva2, Roberto S Dias1
1Molecular Immunovirology Laboratory, General Biology Department, Universidade Federal de Viçosa, Viçosa 36570-900, MG, Brazil.
Abstract:
Mayaro virus (MAYV) is a neglected arthropod-borne virus found in the Americas. MAYV infection results in Mayaro fever, a non-lethal debilitating disease characterized by a strong inflammatory response affecting the joints and muscles. MAYV was once considered endemic to forested areas in Brazil but has managed to adapt and spread to urban regions using new vectors, such as Aedes aegypti, and has the potential to cause serious epidemics in the future. Currently, there are no vaccines or specific treatments against MAYV. In this study, the antiviral activity of a series of synthetic cyclic ketones were evaluated for the first time against MAYV. Twenty-four compounds were screened in a cell viability assay, and eight were selected for further evaluation. Effective concentration (EC50) and selectivity index (SI) were calculated and compound 9-(5-(4-chlorophenyl]furan-2-yl)-3,6-dimethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2))-dione (9) (EC50 = 21.5 µmol·L-1, SI = 15.8) was selected for mechanism of action assays. The substance was able to reduce viral activity by approximately 70% in both pre-treatment and post-treatment assays.
Insights
New synthetic cyclic ketones show promise in fighting Mayaro virus (MAYV). One compound significantly reduced viral activity, offering a potential new avenue for Mayaro fever treatment.
Area of Science:
- Virology
- Medicinal Chemistry
- Epidemiology
Background:
- Mayaro virus (MAYV) is an emerging arthropod-borne virus in the Americas, causing debilitating Mayaro fever with significant inflammatory symptoms.
- MAYV has adapted to urban environments, increasing its epidemic potential, yet no specific treatments or vaccines are currently available.
- The virus's spread and adaptation highlight an urgent need for novel antiviral strategies.
Purpose of the Study:
- To evaluate the antiviral activity of synthetic cyclic ketones against Mayaro virus for the first time.
- To identify potent compounds with high efficacy and low toxicity for potential Mayaro fever therapeutics.
- To investigate the mechanism of action of the most effective compound.
Main Methods:
- Screening of twenty-four synthetic cyclic ketones using cell viability assays.
- Calculation of effective concentration (EC50) and selectivity index (SI) for promising compounds.
- Mechanism of action assays to determine how the lead compound inhibits viral activity.
Main Results:
- Eight out of twenty-four compounds demonstrated significant antiviral activity.
- Compound 9-(5-(4-chlorophenyl]furan-2-yl)-3,6-dimethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2))-dione (9) showed an EC50 of 21.5 µmol·L−1 and an SI of 15.8.
- The lead compound reduced viral activity by approximately 70% in both pre-treatment and post-treatment conditions.
Conclusions:
- Synthetic cyclic ketones represent a promising class of compounds for MAYV antiviral development.
- Compound 9 exhibits potent antiviral activity and a favorable selectivity index, warranting further investigation.
- This study provides a foundation for developing new therapeutic interventions against Mayaro virus infections.
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