Estudio de simulación dinámica y de acoplamiento molecular sobre la prevención de la invasión de glóbulos rojos de merozoitos atacando la proteína de unión al antígeno Duffy de Plasmodium vivax con compuestos bioactivos de Zingiberáceas
DOI:
https://doi.org/10.15359/ru.38-1.18Palabras clave:
Medicamento contra la malaria, en silicio, Plasmodium vivax, PvDBP, ZingiberáceasResumen
Objetivo] Plasmodium vivax infecta ampliamente a muchas personas en algunas regiones. La singularidad de formar una etapa latente hace que la malaria vivax pueda ser inducida por una recaída por una infección adicional. En el presente estudio, utilizamos un enfoque de simulación dinámica y acoplamiento molecular para predecir la posibilidad de que compuestos bioactivos de la familia de plantas Zingiberaceae sean candidatos a fármaco contra la malaria dirigiéndose a la proteína de unión a Duffy de Plasmodium vivax (PvDBP). Se requiere la interacción molecular PvDBP-DARC para mediar el proceso de invasión de merozoitos en los glóbulos rojos. La inhibición de este proceso posiblemente pueda controlar el crecimiento y desarrollo del parásito. [Metodología] El análisis de acoplamiento molecular dio como resultado los dos compuestos principales con el valor de energía de unión más bajo, incluida la 5,7-dihidroxiflavanona (-9,3 kcal/mol) y la pinostrobina (-9,2 kcal/mol). [Resultados] Estos compuestos previstos tienen una interacción más fuerte que la cloroquina como control. Además, los compuestos potenciales también interactúan con los residuos del sitio de unión de DARC y lo mantienen durante el proceso de simulación de dinámica molecular. De lo contrario, la cloroquina como control no puede retener el 75% de los residuos de unión hacia PvDBP. El estudio de dinámica molecular reveló que los tres complejos tienen una estabilidad relativamente similar. [Conclusiones] Predijimos que los dos compuestos bioactivos tienen potencial como inhibidores de la invasión de merozoitos.
Referencias
Abdou A M, Seddek A S, Abdelmageed N, Badry M O and Nishikawa Y. (2022). Wild Egyptian medicinal plants show in vitro and in vivo cytotoxicity and antimalarial activities. BMC Complementary Medicine and Therapies, 22(1), 130. https://doi.org/10.1186/s12906-022-03566-5
Adams J H, Hudson D E, Torii M, Ward G E, Wellems T E, Aikawa M and Miller L H. (1990). The duffy receptor family of Plasmodium knowlesi is located within the micronemes of invasive malaria merozoites. Cell, 63(1), 141–153. https://doi.org/10.1016/0092-8674(90)90295-P
Ahmed M A, Ameyaw E O, Ackah-Armah F, Acheampong D O, Amoani B, Ampomah P, Adakudugu E A and Adokoh C K. (2022). In vitro and In vivo antimalarial activities of Avicennia africana P. Beauv. (Avicenniaceae) ethanolic leaf extract. Journal of Traditional and Complementary Medicine, 12(4), 391–401. https://doi.org/10.1016/j.jtcme.2021.11.004
Arnold G E and Ornstein R L.(1997). Molecular dynamics study of time-correlated protein domain motions and molecular flexibility: Cytochrome P450BM-3. Biophysical Journal, 73(3), 1147–1159. https://doi.org/10.1016/S0006-3495(97)78147-5
Ashar MSAA, Putra WE, Rifa’i M, Sustiprijatno, Salma WO, Susanto H, Faisal M, Hidayatullah A, Heikal MF, Sholeh M. (2023). Calculating the stability of molecular interface between the ligand-complex and solvent molecule: A study of Averrhoa bilimbi bioactive compounds as anti-diabetic agent. AIP Conference Proceedings 2634, 020023. https://doi.org/10.1063/5.0111215.
Atun S, Arianingrum R, Sulistyowati E and Aznam N. (2013). Isolation and antimutagenic activity of some flavanone compounds from Kaempferia rotunda. International Journal of Chemical and Analytical Science, 4(1): 3–8. https://doi.org/10.1016/j.ijcas.2013.03.004
Batchelor J D, Malpede B M, Omattage N S, DeKoster G T, Henzler-Wildman, K A and Tolia N H. (2014). Red Blood Cell Invasion by Plasmodium vivax: Structural Basis for DBP Engagement of DARC. PLoS Pathogens, 10(1), 908-914. https://doi.org/10.1371/journal.ppat.1003869
Batchelor J D, Zahm J A and Tolia N H. (2011). Dimerization of Plasmodium vivax DBP is induced upon receptor binding and drives recognition of DARC. Nature Structural & Molecular Biology, 18(8), 908–914. https://doi.org/10.1038/nsmb.2088
Battle K E and Baird J K. (2021). The global burden of Plasmodium vivax malaria is obscure and insidious. PLOS Medicine, 18(10), 1-18. https://doi.org/10.1371/journal.pmed.1003799
Candotti M, Pérez A, Ferrer-Costa C, Rueda M, Meyer T, Gelpí J L and Orozco M. (2013). Exploring Early Stages of the Chemical Unfolding of Proteins at the Proteome Scale. PLoS Computational Biology, 9(12), e1003393. https://doi.org/10.1371/journal.pcbi.1003393
Castro-Alvarez A, Costa A and Vilarrasa J. (2017). The Performance of Several Docking Programs at Reproducing Protein–Macrolide-Like Crystal Structures. Molecules, 22(1), 136. https://doi.org/10.3390/molecules22010136
Cavasotto CN, Scardino V. (2022). Machine learning toxicity prediction: latest advances by toxicity end point. ACS Omega, 7(51), 47536-47546. https://doi.org/10.1021/acsomega.2c05693
Chootong P, Ntumngia F B, VanBuskirk K M, Xainli J, Cole-Tobian J L, Campbell C O, Fraser T S, King C L and Adams J H. (2010). Mapping Epitopes of the Plasmodium vivax Duffy Binding Protein with Naturally Acquired Inhibitory Antibodies. Infection and Immunity, 78(3), 1089–1095. https://doi.org/10.1128/IAI.01036-09
Chu C S and White N J. (2021). The prevention and treatment of Plasmodium vivax malaria. PLOS Medicine, 18(4), 1-21. https://doi.org/10.1371/journal.pmed.1003561
Dini S, Douglas N M, Poespoprodjo J R, Kenangalem E, Sugiarto P, Plumb I D, Price R N and Simpson J A. (2020). The risk of morbidity and mortality following recurrent malaria in Papua, Indonesia: A retrospective cohort study. BMC Medicine, 18(1), 1-12. https://doi.org/10.1186/s12916-020-1497-0
Ferreira M U, Nobrega de Sousa T, Rangel G W, Johansen I C, Corder R M, Ladeia-Andrade S and Gil J P. (2021). Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions. International Journal for Parasitology: Drugs and Drug Resistance, 15, 9–24. https://doi.org/10.1016/j.ijpddr.2020.12.001
Fraser T, Michon P, Barnwell J W, Noe A R, Al-Yaman F, Kaslow D C and Adams J H. (1997). Expression and serologic activity of a soluble recombinant Plasmodium vivax Duffy binding protein. Infection and Immunity, 65(7), 2772–2777. https://doi.org/10.1128/iai.65.7.2772-2777.1997
Frimurer T M, Peters G H, Iversen L F, Andersen H S, Møller N P H and Olsen O H. (2003). Ligand-Induced Conformational Changes: Improved Predictions of Ligand Binding Conformations and Affinities. Biophysical Journal, 84(4), 2273–2281. https://doi.org/10.1016/S0006-3495(03)75033-4
Gao Y, Mei Y and Zhang J Z H. (2015). Treatment of Hydrogen Bonds in Protein Simulations. In J. Liu (Ed.), Advanced Materials for Renewable Hydrogen Production, Storage and Utilization, 25, 121-136. https://doi.org/10.5772/61049
Getachew S, Thriemer K, Auburn S, Abera A, Gadisa E, Aseffa A, Price R N and Petros B. (2015). Chloroquine efficacy for Plasmodium vivax malaria treatment in southern Ethiopia. Malaria Journal, 14(1), 1-8. https://doi.org/10.1186/s12936-015-1041-4
Han J H, Lee S K, Wang B, Muh F, Nyunt M H, Na S, Ha K S, Hong S H, Park W S, Sattabongkot J, Tsuboi T and Han E T. (2016). Identification of a reticulocyte-specific binding domain of Plasmodium vivax reticulocyte-binding protein 1 that is homologous to the PfRh4 erythrocyte-binding domain. Scientific Reports, 6(1), 1-12. https://doi.org/10.1038/srep26993
Hans D, Pattnaik P, Bhattacharyya A, Shakri A R, Yazdani S S, Sharma M, Choe H, Farzan, M and Chitnis C E. (2005). Mapping binding residues in the Plasmodium vivax domain that binds Duffy antigen during red cell invasion: Binding residues of P. vivax Duffy binding protein. Molecular Microbiology, 55(5), 1423–1434. https://doi.org/10.1111/j.1365-2958.2005.04484.x
Heikal MF, Putra WE, Sustiprijatno, Rifa'i M, Hidayatullah A, Ningsih FN, Widiastuti D, Shuib AS, Zulfiani BF, Hanasepti AF. (2023). In silico screening and molecular dynamics simulation of potential anti-malarial agents from Zingiberaceae as potential Plasmodium falciparum lactate dehydrogenase (PfLDH) enzyme inhibitors. Tropical Life Sciences Research, 34(2), 1-20. https://doi.org/10.21315/tlsr2023.34.2.1
Hidayatullah A, Putra WE, Rifa’i M, Sustiprijatno, Widiastuti D, Heikal MF, Susanto H, Salma WO. (2022). Molecular docking and dynamics simulation studies to predict multiple medicinal plants’ bioactive compounds interaction and its behavior on the surface of DENV-2 E protein. Karbala International Journal of Modern Science, 8(3), 531-542. https://doi.org/10.33640/2405-609X.3237
Hidayatullah A, Putra WE, Salma WO, Muchtaromah B, Permatasari GW, Susanto H, Widiastuti D, Kismurtono M. (2021). Discovery of drug candidate from various natural products as potential novel dengue virus nonstructural protein 5 (NS5) inhibitor. Chiang Mai University Journal of Natural Sciences, 20(1), 1-17. https://doi.org/10.12982/CMUJNS.2021.018
Hidayatullah A, Putra WE, Sustiprijatno, Permatasari GW, Salma WO, Widiastuti D, Susanto H, Muchtaromah B, Sari DRT, Ningsih FN, Heikal MF, Yusuf AMR, Arizona AS. (2021). In silico targeting DENV2's prefusion envelope protein by several natural products' bioactive compounds. Chiang Mai University Journal of Natural Sciences, 20(4), 1-20.
Hidayatullah A, Putra WE, Sustiprijatno, Widiastuti D, Salma WO, Heikal MF. (2023). Molecular docking and molecular dynamics simulation-based identification of natural inhibitors against druggable human papilloma virus type 16 target. Trends in Sciences, 20(4), 1-12. https://doi.org/10.48048/tis.2023.4891
Howes R E, Battle K E, Mendis K N, Smith D L, Cibulskis R E, Baird J K and Hay S I. (2016). Global Epidemiology of Plasmodium vivax. The American Journal of Tropical Medicine and Hygiene, 95(6), 15–34. https://doi.org/10.4269/ajtmh.16-0141
Htun M W, Mon N C N, Aye K M, Hlaing C M, Kyaw M P, Handayuni I, Trimarsanto H, Bustos D, Ringwald P, Price R N, Auburn S and Thriemer K. (2017). Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow. Malaria Journal, 6(1), 281. https://doi.org/10.1186/s12936-017-1912-y
Hubbard R E and Kamran Haider M. (2010). Hydrogen Bonds in Proteins: Role and Strength. In John Wiley & Sons, Ltd (Ed.) ELS (1st ed.). Wiley. https://doi.org/10.1002/9780470015902.a0003011.pub2
Kanchanapiboon J, Kongsa U, Pattamadilok D, Kamponchaidet S, Wachisunthon D, Poonsatha S and Tuntoaw S. (2020). Boesenbergia rotunda extract inhibits Candida albicans biofilm formation by pinostrobin and pinocembrin. Journal of Ethnopharmacology, 261, 1-9. https://doi.org/10.1016/j.jep.2020.113193
Kasahara K, Fukuda I and Nakamura H. (2014). A Novel Approach of Dynamic Cross Correlation Analysis on Molecular Dynamics Simulations and Its Application to Ets1 Dimer–DNA Complex. PLoS ONE, 9(11), 1-13. https://doi.org/10.1371/journal.pone.0112419
Korsinczky M, Fischer K, Chen N, Baker J, Rieckmann K and Cheng Q. (2004). Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site. Antimicrobial Agents and Chemotherapy, 48(6), 2214–2222. https://doi.org/10.1128/AAC.48.6.2214-2222.2004
Lipinski C A. (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
Markus M B. (2011). Malaria: Origin of the Term “Hypnozoite.” Journal of the History of Biology 44(4), 781–786. https://doi.org/10.1007/s10739-010-9239-3
Maslikah SI, Putra WE. (2024). Molecular dynamics simulation of various bioactive compounds of red betel (Piper crocatum) as anti-inflammatory drug-like candidates in rheumatoid arthritis treatment. Trends in Sciences, 21(3), 1-8. https://doi.org/10.48048/tis.2024.7334
Melaku Y, Solomon M, Eswaramoorthy R, Beifuss U, Ondrus V and Mekonnen Y. (2022). Synthesis, antiplasmodial activity and in silico molecular docking study of pinocembrin and its analogs. BMC Chemistry, 16(1), 36. https://doi.org/10.1186/s13065-022-00831-z
Moore L R, Fujioka H, Williams P S, Chalmers J J, Grimberg B, Zimmerman P A and Zborowski M. (2006). Hemoglobin degradation in malaria‐infected erythrocytes determined from live cell magnetophoresis. The FASEB Journal, 20(6), 747–749. https://doi.org/10.1096/fj.05-5122fje
Morikawa T, Funakoshi K, Ninomiya K, Yasuda D, Miyagawa K, Matsuda H and Yoshikawa M. (2008). Medicinal Foodstuffs. XXXIV.1) Structures of New Prenylchalcones and Prenylflavanones with TNF-α and Aminopeptidase N Inhibitory Activities from Boesenbergia rotunda. Chemical and Pharmaceutical bulletin, 56(7), 956-962. https://doi.org/10.1248/cpb.56.956
Okokon J E, Mobley R, Edem U A, Bassey A I, Fadayomi I, Drijfhout F, Horrocks P and Li W W. (2022). In vitro and in vivo antimalarial activity and chemical profiling of sugarcane leaves. Scientific Reports, 12(1), 1-13. https://doi.org/10.1038/s41598-022-14391-8
Ould Ahmedou Salem M S, Mohamed Lemine Y O, Deida J M, Lemrabott M A O, Ouldabdallahi M, Ba M, dit D, Boukhary A O M S, Khairy M L O, Abdel Aziz M B, Ringwald P, Basco L K, Niang S D and Lebatt S M. (2015). Efficacy of chloroquine for the treatment of Plasmodium vivax in the Saharan zone in Mauritania. Malaria Journal, 14(1), 1-5. https://doi.org/10.1186/s12936-015-0563-0
Pishchany G and Skaar E P. (2012). Taste for Blood: Hemoglobin as a Nutrient Source for Pathogens. PLoS Pathogens, 8(3), 1-14. https://doi.org/10.1371/journal.ppat.1002535
Putra WE, Rifa’i M. (2020). Evaluating the molecular interaction of sambucus plant bioactive compounds toward TNF-R1 and TRAIL-R1/R2 as possible anti-cancer therapy based on traditional medicine: The bioinformatics study. Scientific Study & Research - Chemistry & Chemical Engineering, Biotechnology, Food Industry, 21(3), 357-365.
Putra WE, Salma WO, Rifa’i M. (2019). Anti-inflammatory activity of sambucus plant bioactive compounds against TNF-α and TRAIL as solution to overcome inflammation associated diseases: The insight from bioinformatics study. Natural Product Sciences, 25(3), 215-221. https://doi.org/10.20307/nps.2019.25.3.215
Putra WE, Salma WO, Widiastuti D, Kismurtono M. (2020). In silico screening of peroxisome proliferator activated receptor gamma (PPARG)-agonist from Eugenia jambolana bioactive compounds as potential anti-diabetic agent. Malaysian Journal of Biochemistry & Molecular Biology, 23(2), 142-146.
Putra WE, Sustiprijatno, Hidayatullah A, Heikal MF, Widiastuti D, Isnanto H. (2023). Analysis of three non-structural proteins, Nsp1, Nsp2, and Nsp10 of Sars-Cov-2 as pivotal target proteins for computational drug screening. Journal of Microbiology, Biotechnology and Food Sciences, 12(5), 1-6. https://doi.org/10.55251/jmbfs.9586
Putra WE, Waffareta E, Ardiana O, Januarisasi ID, Soewondo A, Rifa'i M. (2017). Dexamethasone-administrated BALB/c mouse promotes proinflammatory cytokine expression and reduces CD4+CD25+ regulatory T cells population. Bioscience Research, 2017. 14(2), 201-213.
Putra WE. (2018). In silico study demonstrates multiple bioactive compounds of sambucus plant promote death cell signaling pathway via Fas receptor. FUW Trends in Science & Technology Journal, 3(2), 682-685.
Ratcliff A, Siswantoro H, Kenangalem E, Maristela R, Wuwung R, Laihad F, Ebsworth E, Anstey N, Tjitra E and Price R. (2007). Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: An open-label randomised comparison. The Lancet, 369(9563), 757–765. https://doi.org/10.1016/S0140-6736(07)60160-3
Sari AN, Putra WE, Rifa’i M, Sustiprijatno, Susanto H, Salma WO, Faisal M, Hidayatullah A, Heikal MF, Firdaus SRA. (2023). Profiling the coulomb energy of chimanine D and desulphosinigrin as potential anti-diabetic drug against alpha-glucosidase. AIP Conference Proceedings 2634, 020012. https://doi.org/10.1063/5.0111214
Sharma B, Chenthamarakshan V, Dhurandhar A, Pereira S, Hendler JA, Dordick JS, Das P. (2023). Accurate clinical toxicity prediction using multi-task deep neural nets and contrastive molecular explanations. Scientific Reports, 13(1), 1-16. https://doi.org/10.1038/s41598-023-31169-8
Singh S K, Singh A P, Pandey S, Yazdani S S, Chitnis C E and Sharma A. (2003). Definition of structural elements in Plasmodium vivax and P. knowlesi Duffy-binding domains necessary for erythrocyte invasion. Biochemical Journal, 374(1), 193–198. https://doi.org/10.1042/bj20030622
Sun H, Nguyen K, Kerns E, Yan Z, Yu KR, Shah P, Jadhav A, Xu X. (2017). Highly predictive and interpretable models for PAMPA permeability. Bioorganic & Medicinal Chemistry, 25(3), 1266-1276. https://doi.org/10.1016/j.bmc.2016.12.049
Sutanto I, Endawati D, Ling L H, Laihad F, Setiabudy R and Baird J K. (2010). Evaluation of chloroquine therapy for vivax and falciparum malaria in southern Sumatra, western Indonesia. Malaria Journal, 9(1), 52. https://doi.org/10.1186/1475-2875-9-52
Tewtrakul S, Subhadhirasakul S and Kummee S. (2005). HIV-1 protease inhibitory effects of medicinal plants used as self medication by AIDS patients. Songklanakarin Journal of Science and Technology, 25(2), 239-243
Widiastuti D, Warnasih S, Sinaga SE, Pujiyawati E, Supriatno, Putra WE. (2023). Identification of active compounds from Averrhoa bilimbi L. (Belimbing Wuluh) flower using LC-MS and antidiabetic activity test using in vitro and in silico approaches. Trends in Sciences, 20(8), 1-9. https://doi.org/10.48048/tis.2023.6761
World Health Organization. (2020). World Malaria Report: 20 years of global progress and challenges. World Health Organization.
Zhu J, Lv Y, Han X, Xu D and Han W. (2017). Understanding the differences of the ligand binding/unbinding pathways between phosphorylated and non-phosphorylated ARH1 using molecular dynamics simulations. Scientific Reports, 7(1), 1-14. https://doi.org/10.1038/s41598-017-12031-0
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