Antiviral effect of compounds derived from the seeds of Mammea americana and Tabernaemontana cymosa on Dengue and Chikungunya virus infections

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.

Phytochemicals as Antiviral Agents: Recent Updates

“…Fisetin was successfully reported to inhibit the replication of dengue virus and enterovirus A71 in vitro (Min et al 2018). The inhibition of hepatitis C virus and the human (2016), Gómez-Calderón et al (2017) cytomegalovirus (HCMV) infection was done by the activity of quercetagetin (Zakaryan et al 2017). Moreover, baicalein, quercetagetin, and fisetin were also reported for the inhibition of chikungunya virus by impeding the intracellular viral replication at early stages (Lani et al 2016).…”

Antivirals Against Chikungunya Virus: Is the Solution in Nature?

“…Among them, antiviral research based on natural molecules is a potential approach. Many natural compounds showed antiviral activity against a variety of human viruses such as dengue (DENV) [22][23][24][25], yellow fever (YFV) [25][26][27], hepatitis C (HCV) [28][29][30][31][32], influenza [33,34], and zika (ZIKV) [33,35,36]. Here, we aim to summarize the natural compounds previously described to possess anti-CHIKV activity ( Table 1).…”

Vaccine and Therapeutic Options To Control Chikungunya Virus

“…Epigallocatechin gallate interfered with CHIKV attachment to and entry into HEK293T cells, while high doses of vitamin C delivered intravenously resolved symptoms in a single CHIKV-infected patient with shoulder and knee pain. A number of additional recent studies have further examined the role of natural products, particularly those derived from plants, seeds, and spices, in generating anti-CHIKV activity (98)(99)(100)(101)(102)(103). Even though some of these products have been used as traditional medicines, their modes of action are not always known.…”