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ANTIVIRALS FOR YELLOW FEVER: BIOASSAY-GUIDED FRACTIONATION OF HIPPEASTRUM PUNICEUM BULB EXTRACT WITH INHIBITORY ACTIVITY AGAINST WILD-TYPE YELLOW FEVER VIRUS AND IN SILICO ADMET PREDICTION OF THE ANNOTATED NATURAL COMPOUNDS
Flores-Souza, Eliza et al. | Date Issued: 2024
Author
Flores-Souza, Eliza
Caldeira, Alisson Samuel Portes
Mazaro, Carolina Colombelli Pacca
Souza, Tamiris Vanessa Miguel de
Acácio, Thaís Magalhães
Barbosa, Emerson de Castro
Pires, Douglas Eduardo Valente
Tavares, Naiara Clemente
Silva, Carlos Eduardo Calzavara
Zani, Carlos Leomar
Oliveira, Jaquelline Germano de
Alves, Tânia Maria de Almeida
Affilliation
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa de Produtos Naturais Bioativos. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa de Produtos Naturais Bioativos. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil
School of Computing and Information Systems. The University of Melbourne. Melbourne, Australia
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa de Produtos Naturais Bioativos. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa de Produtos Naturais Bioativos. Belo Horizonte, MG, Brasil
Abstract
Despite effective vaccines, yellow fever outbreaks persist, increasing the urgency to find antivirals for patient treatment. This study aimed to discover compounds with potential antiviral properties against the wild-type yellow fever virus (wt-YFV) in Hippeastrum puniceum, of the Amaryllidaceae family, through bioassay-guided fractionation of the crude bulb extract using ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution ESI-QTOF mass spectrometry and subsequent analysis of the pharmacokinetic and toxicological properties (ADMET) of the annotated compounds. In the active fractions against wt-YFV, six alkaloids were proposed such as bulbisine, cathinone, trigonelline, tetrahydroharman-3- carboxylic acid, and 2,7-dimethoxyhomolycorine (or 3-O-acetylnarcissidine). Co-occurring in these fractions were the amino acids arginine, asparagine, tryptophan, and glutamic acid. In silico ADMET analysis of the alkaloids predicted good absorption, distribution, excretion, favorable metabolization profiles, and non- mutagenic toxicity, indicating their potential for drug development. These findings justify further in vitro assessment of the compounds against YFV and in vivo testing in animal models. This strategy seems to be an efficient approach for discovering antiviral compounds against YFV. Such discoveries hold promise not only in combating YFV but also in addressing a spectrum of other flaviviruses.
Keywords in Portuguese
Antivirais
Febre amarela
Compostos naturais
 
Keywords
Antivirals
Wild-type yellow fever virus
Hippeastrum puniceum
Natural compound
Bioassay-guided fractionation
UHPLC-HRMS/MS
In silico ADMET prediction
 
Citation
FLORES-SOUZA, Eliza et al. Antivirals for Yellow Fever: Bioassay-Guided Fractionation of Hippeastrum puniceum Bulb Extract with Inhibitory Activity against Wild-Type Yellow Fever Virus and In Silico ADMET Prediction of the Annotated Natural Compounds. 2024. Preprints 2024, 2024071704.