Journal Article

Evaluation of Antiviral Activity of Cyclic Ketones against Mayaro Virus

da Silva, Milene L., Dias, Roberto S., Silva, Cynthia C., de Paula, Sérgio O., Fernandes, Luciana S., Teixeira, Róbson R., da Silva, Ítalo E. P., da S. Lucindo, Marcel S.

2021

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Aedes - virology / Aedes aegypti / Alphavirus - drug effects / Alphavirus - physiology / Alphavirus Infections - drug therapy / Alphavirus Infections - transmission / Alphavirus Infections - virology / Animals / Antiviral activity / Antiviral Agents - chemistry / Antiviral Agents - pharmacology / Antiviral drugs / antiviral properties / antivirals / arbovirus / Arthritis / Arthropods / Brazil / Cell viability / Communication / cyclic ketones / Cytotoxicity / Dengue fever / Drug Evaluation, Preclinical / Epidemics / Fever / Humans / Inflammation / Joint diseases / Ketones / Ketones - chemistry / Ketones - pharmacology / Mayaro virus / mechanism of action / Mosquito Vectors - virology / Muscles / Regression analysis / Rural areas / Vectors / viability assays / Viruses / West Nile virus / Xanthene / xanthenodiones / Zika virus