Abstract
BackgroundThe transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. For this reason, the search for compounds with antiviral potential, either as licensed drugs or in natural products, is a research priority. The objective of this study was to identify some of the compounds that are present in Mammea americana (M. americana) and Tabernaemontana cymosa (T. cymosa) plants and, subsequently, to evaluate their cytotoxicity in VERO cells and their potential antiviral effects on DENV and CHIKV infections in those same cells.MethodsDry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa.. The cytotoxicity of each compound was subsequently assessed by the MTT method (at concentrations from 400 to 6.25 μg/mL). Pre- and post-treatment antiviral assays were performed at non-toxic concentrations; the resulting DENV inhibition was evaluated by Real-Time PCR, and the CHIKV inhibition was tested by the plating method. The results were analyzed by means of statistical analysis.ResultsThe compounds showed low toxicity at concentrations ≤ 200 μg/mL. The compounds coumarin A and coumarin B, which are derived from the M. americana plant, significantly inhibited infection with both viruses during the implementation of the two experimental strategies employed here (post-treatment with inhibition percentages greater than 50%, p < 0.01; and pre-treatment with percentages of inhibition greater than 40%, p < 0.01). However, the lupeol acetate and voacangine compounds, which were derived from the T. cymosa plant, only significantly inhibited the DENV infection during the post-treatment strategy (at inhibition percentages greater than 70%, p < 0.01).ConclusionIn vitro, the coumarins are capable of inhibiting infection by DENV and CHIKV (with inhibition percentages above 50% in different experimental strategies), which could indicate that these two compounds are potential antivirals for treating Dengue and Chikungunya fever. Additionally, lupeol acetate and voacangine efficiently inhibit infection with DENV, also turning them into promising antivirals for Dengue fever.
Highlights
The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment
The biological activities of these plants, such as antimicrobial, antiparasitic, antitumoral, antifebrile, analgesic, and antiviral properties, have been widely studied [29, 30], as well as their effects against the larvae and adults of A. aegypti [31]. Taking this background into account, the objective of this study was to identify some of the compounds that are present in the M. americana and T. cymosa plants and to subsequently evaluate their cytotoxicity in VERO cells and their potential antiviral effect on DENV and CHIKV infection in those same cells
Identification of the compounds present in the M. americana and T. cymosa fractions Five fractions were obtained from the M. americana extract (FD-I-34S) and four fractions were obtained from the T. cymosa extract (FD-I-26S)
Summary
The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. The genome encodes a single viral polyprotein that gives rise to three structural proteins designated as the Capsid (C), PreMatrix/Matrix (prM/M), and Envelope (E) and to seven nonstructural proteins designated NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 [8] Each of these proteins fulfills important functions during entry and viral replication in the host cell. The DENV infection process is initiated through the binding of the virus to receptors on the cell surface via the E protein, followed by endocytosis, in which variations in pH trigger the fusion of this protein with the endosomal membrane, releasing the nucleocapsid (RNA bound to the C protein) into the cytoplasm After this release, the transcription process (which generates negative intermediary RNAs and subsequently new positive sense RNA) and translation start in ribosomes associated with the endoplasmic reticulum. The newly generated polyprotein is cleaved by cellular and viral proteases for assembly with the viral RNAs, with new viruses being released by gemmation [9]
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