In Vitro and In Silico Anti-Arboviral Activities of Dihalogenated Phenolic Derivates of L-Tyrosine
| Autor: | Manuel Pastrana Restrepo, Wildeman Zapata, Sergio Andres Pulido Muñoz, Laura Milena Monsalve-Escudero, Vanessa Loaiza-Cano, Elkin Galeano, Diana Carolina Quintero-Gil, Marlen Martinez-Gutierrez |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Halogenation
Viral protein In silico viruses Pharmaceutical Science Genome Viral Molecular Dynamics Simulation Dengue virus medicine.disease_cause Article Cell Line Analytical Chemistry Zika virus 03 medical and health sciences QD241-441 computational biology Phenols Chlorocebus aethiops Drug Discovery antiviral agents medicine Animals Humans Chikungunya Physical and Theoretical Chemistry Vero Cells 030304 developmental biology 0303 health sciences chikungunya virus Molecular Structure biology dengue virus 030306 microbiology Chemistry Organic Chemistry Helicase virus diseases AutoDock Virology In vitro Molecular Docking Simulation Chemistry (miscellaneous) Vero cell biology.protein Molecular Medicine tyrosine |
| Zdroj: | Molecules Molecules, Vol 26, Iss 3430, p 3430 (2021) Volume 26 Issue 11 |
| ISSN: | 1420-3049 |
| Popis: | Despite the serious public health problem represented by the diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses, there are still no specific licensed antivirals available for their treatment. Here, we examined the potential anti-arbovirus activity of ten di-halogenated compounds derived from L-tyrosine with modifications in amine and carboxyl groups. The activity of compounds on VERO cell line infection and the possible mechanism of action of the most promising compounds were evaluated. Finally, molecular docking between the compounds and viral and cellular proteins was evaluated in silico with Autodock Vina®, and the molecular dynamic with Gromacs®. Only two compounds (TDC-2M-ME and TDB-2M-ME) inhibited both ZIKV and CHIKV. Within the possible mechanism, in CHIKV, the two compounds decreased the number of genome copies and in the pre-treatment strategy the infectious viral particles. In the ZIKV model, only TDB-2M-ME inhibited the viral protein and demonstrate a virucidal effect. Moreover, in the U937 cell line infected with CHIKV, both compounds inhibited the viral protein and TDB-2M-ME inhibited the viral genome too. Finally, the in silico results showed a favorable binding energy between the compounds and the helicases of both viral models, the NSP3 of CHIKV and cellular proteins DDC and β2 adrenoreceptor. |
| Databáze: | OpenAIRE |
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