title: Antiviral effect of compounds derived from the seeds of Mammea americana and Tabernaemontana cymosa on Dengue and Chikungunya virus infections.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  Dry 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.
  
  
  RESULTS
  The 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).
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Grupo de Investigación en Ciencias Animales-GRICA, Universidad Cooperativa de Colombia, Calle 30A # 33-51, Bucaramanga, Colombia.|Facultad de Ciencias de la Salud, Programa de Bacteriología y Laboratorio Clínico, Grupo de investigación en manejo clínico - CLINIUDES, Universidad de Santander UDES, Bucaramanga, Colombia.|Maestría en Enfermedades Infecciosas, Universidad de Santander, Bucaramanga, Colombia.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gómez-Calderón
authors.affiliation: Grupo de Investigación en Ciencias Animales-GRICA, Universidad Cooperativa de Colombia, Calle 30A # 33-51, Bucaramanga, Colombia.|PECET, Facultad de Medicina, University of Antioquia, Medellín, Colombia.
authors.forename: Carol
authors.initials: C
authors.lastname: Mesa-Castro
authors.affiliation: PECET, Facultad de Medicina, University of Antioquia, Medellín, Colombia.
authors.forename: Sara
authors.initials: S
authors.lastname: Robledo
authors.affiliation: Facultad de Ciencias de la Salud, Programa de Bacteriología y Laboratorio Clínico, Grupo de investigación en manejo clínico - CLINIUDES, Universidad de Santander UDES, Bucaramanga, Colombia.
authors.forename: Sergio
authors.initials: S
authors.lastname: Gómez
authors.affiliation: Laboratorio de Investigaciones Fotoquímicas y Farmacológicas de la Universidad de Cartagena (LIFFUC), Universidad de Cartagena, Cartagena, Colombia.
authors.forename: Santiago
authors.initials: S
authors.lastname: Bolivar-Avila
authors.affiliation: Laboratorio de Investigaciones Fotoquímicas y Farmacológicas de la Universidad de Cartagena (LIFFUC), Universidad de Cartagena, Cartagena, Colombia.
authors.forename: Fredyc
authors.initials: F
authors.lastname: Diaz-Castillo
authors.affiliation: Grupo de Investigación en Ciencias Animales-GRICA, Universidad Cooperativa de Colombia, Calle 30A # 33-51, Bucaramanga, Colombia. marlen.martinezg@campusucc.edu.co.
authors.forename: Marlen
authors.initials: M
authors.lastname: Martínez-Gutierrez
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D065632:Chikungunya Fever / Q000188:drug therapy*; D002522:Chlorocebus aethiops; D003603:Cytotoxins / Q000633:toxicity; D003715:Dengue / Q000188:drug therapy*; D031252:Mammea / Q000737:chemistry* / Q000633:toxicity; D010936:Plant Extracts / Q000627:therapeutic use* / Q000633:toxicity; D030014:Tabernaemontana / Q000737:chemistry* / Q000633:toxicity; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D003603:Cytotoxins; D010936:Plant Extracts
keywords: Antiviral; Chikungunya Virus; Dengue Virus; Mammea americana; Tabernaemontana cymosa