Evaluación y detección bioinformática de terpenoides con potencial inhibitorio de la proteína viral 1 (VP1) del virus de la bursitis infecciosa
Evaluation and bioinformatic detection of terpenoids with inhibitory potential of viral protein 1 (VP1) of infectious bursitis virus
DOI:
https://doi.org/10.15446/rfmvz.v70n3.106011Keywords:
Bursitis, ARN polimerasa, terpenos, Gumboro (es)bursitis, RNA polymerase, terpenes, Gumboro (en)
Downloads
El virus de la bursitis infecciosa (IBDV) es el agente causal de la enfermedad de la bursa, la cual afecta principalmente a poblaciones avícolas jóvenes y genera un impacto económico negativo en la producción. La proteína vira 1 (VP1) es una enzima con funciones clave para la replicación del genoma viral, por lo que puede ser considerada blanco para la búsqueda de compuestos con posibles actividades inhibitorias. El objetivo de esta investigación fue evaluar terpenoides con potencial inhibitorio de la proteína VP1 del IBDV mediante herramientas de aproximaciones bioinformáticas. Se seleccionó un total de 52 terpenoides, cuyas propiedades farmacológicas, farmacocinéticas y tóxicas (ADME-Tox) se evaluaron. Las moléculas sin actividades tóxicas y con aptitudes farmacocinéticas fueron sometidas a pruebas exhaustivas de acoplamiento molecular con el sitio catalítico de la VP1 mediante el uso del algoritmo genético y de Broyden-Fletcher-Goldfarb-Shanno junto con el método de optimización local de gradientes. Los datos obtenidos revelaron que la Giberelina A1 presenta valores de energía libre de unión significativamente (P < 0,05) favorables (ΔG=-7,28±0,06 kcal/mol; Kdcalc= 8,62±0,99 μM) en comparación con los sustratos rCTP y rGTP. El complejo Giberelina A1-VP1 presenta puentes de hidrógeno con los residuos Arg335 y Asp402, los cuales cumplen roles importantes en la actividad catalítica en la replicación viral. Estos hallazgos sugieren que el terpenoide Giberelina A1 puede ser considerado como compuesto candidato para estudios in vitro de inhibición de funciones de la VP1 e in vivo de actividades antivirales contra el virus de la bursitis infecciosa.
Infectious bursitis virus (IBDV) is the infectious agent of bursal disease, which mainly affects young poultry populations, generating a negative economic impact on productions. The viral protein 1 (VP1) is an enzyme with important functions for the replication of the viral genome, so it could be considered as a target for searching compounds with possible inhibitory activities. The aim of this research was to evaluate terpenoids with inhibitory potential of the VP1 protein of IBDV using computational approximations tools. A total of 52 terpenoids were selected and evaluated for their pharmacological, pharmacokinetic and toxic properties (ADME-Tox). Molecules without toxic activities and with pharmacokinetic competences were subjected to extensive molecular docking tests with the catalytic site of VP1 using the genetic and Broyden-Fletcher-Goldfarb-Shanno algorithms with a local gradient optimization method. Data obtained revealed that Gibberellin A1 exhibits significantly (P < 0.05) favorable binding free energy values (ΔG=-7.28±0.06 kcal/mol; Kdcalc= 8.62±0.99 μM) compared to rCTP and rGTP substrates. The Gibberellin A1-VP1 complex exhibits hydrogen bonds with residues Arg335 and Asp402, which play important roles in catalytic activity in viral replication. These findings suggest that the terpenoid Gibberellin A1 could be considered as a candidate compound for in vitro studies of inhibition of VP1 functions and in vivo antiviral activities against infectious bursitis virus.
References
Ahmad W, Ejaz S, Anwar K, Ashraf M. 2014. Exploration of the in vitro cytotoxic and antiviral activities of different medicinal plants against infectious bursal disease (IBD) virus. Open Life Sciences. 9(5):531–542. https://doi.org/10.2478/s11535-013-0276-8 DOI: https://doi.org/10.2478/s11535-013-0276-8
Amal Gaber SF, Ibrahim N, Yaakob WA. 2014. Phytochemical screening and antiviral activity of Marrubium vulgare. Malaysian Journal of Microbiology. 10(2):106-111. http://dx.doi.org/10.21161/mjm.58013 DOI: https://doi.org/10.21161/mjm.58013
Angeh JE, Huang X, Swan GE, Möllman U, Sattler I, Eloff JN. 2006. Novel antibacterial triterpenoid from Combretum padoides [Combretaceae]. Zhdankin VV, editor. Arkivoc. 2007(9):113-120. https://doi.org/10.3998/ark.5550190.0008.913 DOI: https://doi.org/10.3998/ark.5550190.0008.913
Anyanwu AA, Jimam NS, Omale S, Wannang NN. 2017. Antiviral activities of Cucumis metuliferus fruits alkaloids on Infectious Bursal Disease Virus (IBDV). J Phytopharmacol. 6(2):98-101. https://doi.org/10.31254/phyto.2017.6206 DOI: https://doi.org/10.31254/phyto.2017.6206
Berg TPVD. 2000. Acute infectious bursal disease in poultry: A review. Avian Pathology. 29(3):175-194. https://doi.org/10.1080/03079450050045431 DOI: https://doi.org/10.1080/03079450050045431
Brito S, Crescente O, Fernández A, Coronado A, Rodríguez N. 2006. Eficacia de un ácido kaurénico extraído de la planta venezolana Wedelia trilobata (Asterácea) contra Leishmania (Viannia) braziliensis. Biomedica. 26:180-187. Disponible en: http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-41572006000500019 DOI: https://doi.org/10.7705/biomedica.v26i1.1511
Choudhury A, Das NC, Patra R, Bhattacharya M, Ghosh P, Patra BC, Mukherjee S. 2021. Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach. Future Virology. 16(4):277-291. https://doi.org/10.2217/fvl-2020-0342 DOI: https://doi.org/10.2217/fvl-2020-0342
Chukwuma OJT, Joseph AO, Dike N. 2017. In vitro antiviral activities of Aframomum melegueta leaf extracts on Newcastle Disease Virus (NDV), Fowl Pox Virus (FPV) and Infectious Bursal Disease Virus (IBDV). IDOSR Journal of Science and Technology. 2(2): 33-45. Disponible en: https://www.idosr.org/wp-content/uploads/2017/12/IDOSR-JST-22-33-45-2017-ON-1.pdf
Daina A, Michielin O, Zoete V. 2014. iLOGP: A Simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. J Chem Inf Model. 54(12):3284-3301. https://doi.org/10.1021/ci500467k DOI: https://doi.org/10.1021/ci500467k
Daina A, Michielin O, Zoete V. 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 7(1):42717. https://doi.org/10.1038/srep42717 DOI: https://doi.org/10.1038/srep42717
Daina A, Zoete V. 2016. A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem. 11(11):1117-1121. https://doi.org/10.1002/cmdc.201600182 DOI: https://doi.org/10.1002/cmdc.201600182
Drwal MN, Banerjee P, Dunkel M, Wettig MR, Preissner R. 2014. ProTox: a web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Research. 42(W1):W53-W58. https://doi.org/10.1093/nar/gku401 DOI: https://doi.org/10.1093/nar/gku401
Fricker PC, Gastreich M, Rarey M. 2004. Automated Drawing of Structural Molecular Formulas under Constraints. J Chem Inf Comput Sci. 44(3):1065-1078. https://doi.org/10.1021/ci049958u DOI: https://doi.org/10.1021/ci049958u
Ganesan A. 2008. The impact of natural products upon modern drug discovery. Current Opinion in Chemical Biology. 12(3):306-317. https://doi.org/10.1016/j.cbpa.2008.03.016 DOI: https://doi.org/10.1016/j.cbpa.2008.03.016
Garriga D, Navarro A, Querol–Audí J, Abaitua F, Rodríguez JF, Verdaguer N. 2007. Activation mechanism of a noncanonical RNA-dependent RNA polymerase. Proceedings of the National Academy of Sciences. 104(51):20540-20545. https://doi.org/10.1073/pnas.0704447104 DOI: https://doi.org/10.1073/pnas.0704447104
Gayozo E, Rojas L, Castro L. 2022. Acoplamiento molecular entre la proteína viral 1 del virus de la enfermedad infecciosa bursal y fitoconstituyentes de Withania somnifera (L.) Dunal: Un enfoque computacional. Revista de Investigaciones Veterinarias del Perú. 33(5):e22022-e22022. https://doi.org/10.15381/rivep.v33i5.22022 DOI: https://doi.org/10.15381/rivep.v33i5.22022
Ghisalberti EL. 1997. The biological activity of naturally occurring kaurane diterpenes. Fitoterapia, 68(4), 303-325. Disponible en: https://api.semanticscholar.org/CorpusID:88747041
Hammer O, Harper DAT, Ryan PD. 2001. PAST: Paleontological Statistics Software Package for Education and Data Analysis 4(1):1-9. Disponible en: http://palaeo-electronica.org/2001_1/past/issue1_01.htm
Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. 2012. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. Journal of Cheminformatics. 4(1):17. https://doi.org/10.1186/1758-2946-4-17 DOI: https://doi.org/10.1186/1758-2946-4-17
Jumaa RS, Abdulmajeed DI, Karim AJ. 2021. Evaluation of secondary metabolites of herbal plant extracts as an antiviral effect on infectious bursal disease virus isolates in embryonated chicken eggs. Vet World. 14(11):2971-2978. https://doi.org/10.14202/vetworld.2021.2971-2978 DOI: https://doi.org/10.14202/vetworld.2021.2971-2978
Lipinski CA. 2004. Lead and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies. 1(4):337-341. https://doi.org/10.1016/j.ddtec.2004.11.007 DOI: https://doi.org/10.1016/j.ddtec.2004.11.007
Ludwiczuk A, Skalicka-Woźniak K, Georgiev MI. 2017. Chapter 11. Terpenoids. En: Badal S, Delgoda R, editores. Pharmacognosy. Boston: Academic Press. p. 233–266. Disponible en: https://www.sciencedirect.com/science/article/pii/B9780128021040000111 DOI: https://doi.org/10.1016/B978-0-12-802104-0.00011-1
Nosrati M, Behbahani M. 2015. Molecular docking study of HIV-1 protease with triterpenoides compounds from plants and mushroom. Arak Uni Med Sci J. 18(3): 67-79. Disponible en: http://jams.arakmu.ac.ir/article-1-3723-en.html
Pant M, Ambwani T, Umapathi V. 2012. Antiviral activity of ashwagandha extract on infectious bursal disease virus replication. Indian Journal of Science and Technology. 5(5): 2750-2751. https://doi.org/10.17485/ijst/2012/v5i5.20 DOI: https://doi.org/10.17485/ijst/2012/v5i5.20
Pérez JR, Ramos CS, Gamboa AV, Cabarcos NP, Murgas GF. 2009. Uso de microdosis de aloe vera L. en el asma bronquial. Medicina Naturista. 3(2):66-71.
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. 2004. UCSF Chimera. A visualization system for exploratory research and analysis. Journal of Computational Chemistry. 25(13):1605-1612. https://doi.org/10.1002/jcc.20084 DOI: https://doi.org/10.1002/jcc.20084
Poroikov VV. 2020. Computer-aided drug design: from discovery of novel pharmaceutical agents to systems pharmacology. Biochem Moscow Suppl Ser B. 14(3):216-227. https://doi.org/10.1134/S1990750820030117 DOI: https://doi.org/10.1134/S1990750820030117
Saboon, Chaudhari SK, Arshad S, Amjad MS, Akhtar MS. 2019. Natural Compounds Extracted from Medicinal Plants and Their Applications. En: Akhtar MS, Swamy MK, Sinniah UR, editores. Natural Bio-active Compounds. Volume 1. Production and Applications. Singapore: Springer. p. 193–207. https://doi.org/10.1007/978-981-13-7154-7_7 DOI: https://doi.org/10.1007/978-981-13-7154-7_7
Sharma JM, Kim IJ, Rautenschlein S, Yeh HY. 2000. Infectious bursal disease virus of chickens: pathogenesis and immunosuppression. Developmental & Comparative Immunology. 24(2):223-235. https://doi.org/10.1016/S0145-305X(99)00074-9 DOI: https://doi.org/10.1016/S0145-305X(99)00074-9
Stierand K, Maaß PC, Rarey M. 2006. Molecular complexes at a glance: automated generation of two-dimensional complex diagrams. Bioinformatics. 22(14):1710-1716. https://doi.org/10.1093/bioinformatics/btl150 DOI: https://doi.org/10.1093/bioinformatics/btl150
Sun Y, Song M, Niu L, Bai X, Sun N, Zhao X, Jiang J, He J, Li H. 2013. Antiviral effects of the constituents derived from Chinese herb medicines on infectious bursal disease virus. Pharmaceutical Biology. 51(9):1137-1143. https://doi.org/10.3109/13880209.2013.781197 DOI: https://doi.org/10.3109/13880209.2013.781197
Trott O, Olson AJ. 2010. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry. 31(2):455-461. https://doi.org/10.1002/jcc.21334 DOI: https://doi.org/10.1002/jcc.21334
Volkamer A, Griewel A, Grombacher T, Rarey M. 2010. Analyzing the topology of active sites: on the prediction of pockets and subpockets. J Chem Inf Model. 50(11):2041-2052. https://doi.org/10.1021/ci100241y DOI: https://doi.org/10.1021/ci100241y
Volkamer A, Kuhn D, Grombacher T, Rippmann F, Rarey M. 2012. Combining Global and Local Measures for Structure-Based Druggability Predictions. J Chem Inf Model. 52(2):360-372. https://doi.org/10.1021/ci200454v DOI: https://doi.org/10.1021/ci200454v
Yang JL, Ha TKQ, Dhodary B, Pyo E, Nguyen NH, Cho H, Kim E, Oh WK. 2015. Oleanane Triterpenes from the Flowers of Camellia japonica Inhibit Porcine Epidemic Diarrhea Virus (PEDV) Replication. J Med Chem. 58(3):1268-1280. https://doi.org/10.1021/jm501567f DOI: https://doi.org/10.1021/jm501567f
Yang W, Chen X, Li Y, Guo S, Wang Z, Yu X. 2020. Advances in Pharmacological Activities of Terpenoids. Natural Product Communications. 15(3):1-13. https://doi.org/10.1177/1934578X20903555 DOI: https://doi.org/10.1177/1934578X20903555
How to Cite
APA
ACM
ACS
ABNT
Chicago
Harvard
IEEE
MLA
Turabian
Vancouver
Download Citation
License
Copyright (c) 2023 Revista de la Facultad de Medicina Veterinaria y de Zootecnia
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© Facultad de Medicina Veterinaria y de Zootecnia, Universidad Nacional de Colombia.
Copying and citation of materials that appear in the Journal are authorized as long as a clear statement indicates the journal title, author(s) name(s), year of publication, volume, and the number of pages of the article cited.