Searching for plant-derived antivirals against dengue virus and Zika virus

dc.creatorBarbosa, Emerson de Castro
dc.creatorAlves, Tânia Maria Almeida
dc.creatorKohlhoff, Markus
dc.creatorJangola, Soraya Torres Gaze
dc.creatorPires, Douglas Eduardo Valente
dc.creatorFigueiredo, Anna Carolina Cançado
dc.creatorAlves, Érica Alessandra Rocha
dc.creatorSilva, Carlos Eduardo Calzavara
dc.creatorSobral, Marcos
dc.creatorKroon, Erna Geessien
dc.creatorRosa, Luiz Henrique
dc.creatorZani, Carlos Leomar
dc.creatorOliveira, Jaquelline Germano de
dc.date2022-12-22T13:02:13Z
dc.date2022-12-22T13:02:13Z
dc.date2022
dc.date.accessioned2023-09-26T20:49:30Z
dc.date.available2023-09-26T20:49:30Z
dc.identifierBARBOSA, Emerson de Castro et al. Searching for plant-derived antivirals against dengue virus and Zika vírus. Virol J., v. 19, n. 1, 31, 2022. doi: 10.1186/s12985-022-01751-z.
dc.identifier1743-422X
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/56155
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8864541
dc.descriptionBackground: The worldwide epidemics of diseases as dengue and Zika have triggered an intense effort to repurpose drugs and search for novel antivirals to treat patients as no approved drugs for these diseases are currently available. Our aim was to screen plant-derived extracts to identify and isolate compounds with antiviral properties against dengue virus (DENV) and Zika virus (ZIKV). Methods: Seven thousand plant extracts were screened in vitro for their antiviral properties against DENV-2 and ZIKV by their viral cytopathic effect reduction followed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, previously validated for this purpose. Selected extracts were submitted to bioactivity-guided fractionation using high- and ultrahigh-pressure liquid chromatography. In parallel, high-resolution mass spectrometric data (MSn) were collected from each fraction, allowing compounds into the active fractions to be tracked in subsequent fractionation procedures. The virucidal activity of extracts and compounds was assessed by using the plaque reduction assay. EC50 and CC50 were determined by dose response experiments, and the ratio (EC50/CC50) was used as a selectivity index (SI) to measure the antiviral vs. cytotoxic activity. Purified compounds were used in nuclear magnetic resonance spectroscopy to identify their chemical structures. Two compounds were associated in different proportions and submitted to bioassays against both viruses to investigate possible synergy. In silico prediction of the pharmacokinetic and toxicity (ADMET) properties of the antiviral compounds were calculated using the pkCSM platform. Results: We detected antiviral activity against DENV-2 and ZIKV in 21 extracts obtained from 15 plant species. Hippeastrum (Amaryllidaceae) was the most represented genus, affording seven active extracts. Bioactivity-guided fractionation of several extracts led to the purification of lycorine, pretazettine, narciclasine, and narciclasine-4-O-β-D-xylopyranoside (NXP). Another 16 compounds were identified in active fractions. Association of lycorine and pretazettine did not improve their antiviral activity against DENV-2 and neither to ZIKV. ADMET prediction suggested that these four compounds may have a good metabolism and no mutagenic toxicity. Predicted oral absorption, distribution, and excretion parameters of lycorine and pretazettine indicate them as candidates to be tested in animal models. Conclusions: Our results showed that plant extracts, especially those from the Hippeastrum genus, can be a valuable source of antiviral compounds against ZIKV and DENV-2. The majority of compounds identified have never been previously described for their activity against ZIKV and other viruses.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBioMed Central
dc.rightsopen access
dc.subjectAlkaloids
dc.subjectAntiviral; Bioactivity-guided fractionation
dc.subjectCompounds
dc.subjectDengue virus
dc.subjectHippeastrum
dc.subjectNatural products
dc.subjectPlant extract
dc.subjectVirucidal
dc.subjectZika virus
dc.titleSearching for plant-derived antivirals against dengue virus and Zika virus
dc.typeArticle


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