Estudio in silico de fitoquímicos en la región del Receptor-Binding Domain (RBD) de la proteína spike del SARS-CoV-2 (variante Omicron, B.1.1.529)
DOI:
https://doi.org/10.33448/rsd-v11i10.33126Palabras clave:
Covid-19; Acoplamiento molecular; Moléculas naturales.Resumen
El COVID-19 es una enfermedad altamente contagiosa causada por el síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2) convirtiéndose en una gran amenaza a nivel mundial debido a su rápida propagación y variantes más agresivas, como es el caso de Omicron. La principal estructura de interacción del virus con la célula huésped es la región de la espiga de la proteína Spike llamada RBD, una estructura que ha tenido varias mutaciones, lo que dificulta la búsqueda de fármacos. Con base en este escenario, el presente trabajo tuvo como objetivo evaluar el perfil de interacciones entre moléculas de origen natural contra la región RBD de la proteína Spike (S) del SARS-CoV-2, variante Ômicron. En el primer paso metodológico, hubo un modelado molecular de la estructura RBD de una secuencia obtenida en Brasil y pruebas para su caracterización y validación estructural. Luego, se realizó acoplamiento molecular entre 6 ligandos fitoquímicos: Curcumina, Carvacrol (±)-Limoneno, Glicirricina, Alicina y Quercetina-3-Arabinósido en la región específica modelada RBD, luego de obtener los mejores resultados, los complejos formados fueron evaluados por RMSD y RMSF. En la homología de la región RBD se obtuvo una estructura con bajos errores estructurales. En las interacciones de cada fitoquímico, las moléculas glicirricina y quercetina mostraron mayor afinidad molecular, uniéndose al sitio activo que se encuentra en RBD. La dinámica molecular confirmó la interacción de los ligandos y la estabilidad de los complejos durante las simulaciones. La quercetina y la glicirricina mostraron una molécula potencial que se une a la región RBD de la proteína S, del genoma de la variante omicron sin precedentes del SARS-CoV-2 secuenciada en Brasil.
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Abraham M. J., Murtola T., Schulz R., Páll S., Smith J. C., Hess B., & Lindahl E. (2015). GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1(2), 19–25.
Adhikari, S. P., Meng, S., Wu, Y. J., Mao, Y. P., Ye, R. X., Wang, Q. Z., Sun, C., Sylvia, S., Rozelle, S., Raat, H., & Zhou, H. (2020). Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infectious diseases of poverty, 9(1), 29.
Ahmed, M. Z., Zia, Q., Haque, A., Alqahtani, A. S., Almarfadi, O. M., Banawas, S., Alqahtani, M. S., Ameta, K. L. & Haque, S. (2021). Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in-silico drug repurposing study on FDA-approved antiviral and anti-infection agents. J Infect Public Health. 14(5): 611-9. doi: 10.1016/j.jiph.2021.01.016.
Badshah, S. L., Faisal, S., Muhammad, A., Poulson, B. G., Emwas, A. H., & Jaremko, M. (2021). Antiviral activities of flavonoids. Biomedicine & pharmacotherapy, 140, 111596.
Barca, G., Bertoni, C., Carrington, L., Datta, D., De Silva, N., Deustua, J. E., Fedorov, D. G., Gour, J. R., Gunina, A. O., Guidez, E., Harville, T., Irle, S., Ivanic, J., Kowalski, K., Leang, S. S., Li, H., Li, W., Lutz, J. J., Magoulas, I., Mato, J., Gordon, M. S. (2020). Recent developments in the general atomic and molecular electronic structure system. The Journal of chemical physics, 152(15), 154102.
Batiha, E-S. G., Magdy Beshbishy, A., G Wasef, L., Elewa, Y., A Al-Sagan, A., Abd El-Hack, M. E., Taha, A. E., M Abd-Elhakim, Y., & Prasad Devkota, H. (2020). Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review. Nutrients, 12(3), 872.
Benkert, P., Tosatto, S. C., & Schomburg, D. (2008). QMEAN: A comprehensive scoring function for model quality assessment. Proteins, 71(1), 261–277.
Biasini, M., Bienert, S., Waterhouse, A., Arnold, K., Studer, G., Schmidt, T., Kiefer, F., Cassarino, T. Z., Bertoni, M., Bordoli, L., Schwede, T. (2014). SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 42(W1), W252-W258.
Boehm E., Kronig I., Neher R.A., Eckerle I., Vetter P., Kaiser L. (2021) Novel SARS-CoV-2 variants: the pandemics within the pandemic. Clin. Microbiol. Infect. 27:1109.
Cabanillas, E. R. L., Risco, A. O. L., Risco, K. B. L., Hoyos, G. L. L., Zavaleta, R. M. L., Tirado, E. d. R. L., Saavedra, J. J. H. (2021). Molecular basis of COVID-19 pathogenesis and in silico studies of potential pharmacological treatment. Revista de la Facultad de Medicina Humana, 21(2).
Chen J. (2020). Pathogenicity and transmissibility of 2019-nCoV-A quick overview and comparison with other emerging viruses. Microbes and infection, 22(2), 69–71.
Chen, Y., Liu, Q., & Guo, D. (2020). Emerging coronaviruses: Genome structure, replication, and pathogenesis. Journal of medical virology, 92(4), 418–423.
Christy, M. P., Uekusa, Y., Gerwick, L., & Gerwick, W. H. (2021). Natural Products with Potential to Treat RNA Virus Pathogens Including SARS-CoV-2. Journal of natural products, 84(1), 161–182.
Darden T., York D., & Pedersen L. (1993). Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems. The Journal of Chemical Physics, 98(12), 10089–10092.
Di Pierro, F., Derosa, G., Maffioli, P., Bertuccioli, A., Togni, S., Riva, A., Allegrini, P., Khan, A., Khan, S., Khan, B. A., Altaf, N., Zahid, M., Ujjan, I. D., Nigar, R., Khushk, M. I., Phulpoto, M., Lail, A., Devrajani, B. R., & Ahmed, S. (2021). Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study. International journal of general medicine, 14, 2359–2366.
Dimova, S., Mugabowindekwe, R., Willems, T., Brewster, M. E., Noppe, M., Ludwig, A., Jorissen, M., & Augustijns, P. (2003). Safety-assessment of 3-methoxyquercetin as an antirhinoviral compound for nasal application: effect on ciliary beat frequency. International journal of pharmaceutics, 263(1-2), 95–103.
Dodda, L. S., Cabeza de Vaca, I., Tirado-Rives, J., & Jorgensen, W. L. (2017). LigParGen web server: an automatic OPLS-AA parameter generator for organic ligands. Nucleic acids research, 45(W1), W331–W336.
Eisenberg, D., Lüthy, R., & Bowie, J. U. (1997). VERIFY3D: assessment of protein models with three-dimensional profiles. Methods in enzymology, 277, 396–404.
Elfiky A. A. (2020). Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life sciences, 248, 117477.
Elmezayen, A. D., Al-Obaidi, A., Şahin, A. T., & Yelekçi, K. (2021). Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes. Journal of biomolecular structure & dynamics, 39(8), 2980–2992.
Favalli, E. G., Ingegnoli, F., De Lucia, O., Cincinelli, G., Cimaz, R., & Caporali, R. (2020). COVID-19 infection and rheumatoid arthritis: Faraway, so close!. Autoimmunity reviews, 19(5), 102523.
Gansukh, E., Kazibwe, Z., Pandurangan, M., Judy, G., & Kim, D. H. (2016). Probing the impact of quercetin-7-O-glucoside on influenza virus replication influence. Phytomedicine: international journal of phytotherapy and phytopharmacology, 23(9), 958–967.
Ghosh, R., Chakraborty, A., Biswas, A., & Chowdhuri, S. (2021). Evaluation of green tea polyphenols as novel corona virus (SARS CoV-2) main protease (Mpro) inhibitors - an in silico docking and molecular dynamics simulation study. Journal of biomolecular structure & dynamics, 39(12), 4362–4374.
Glinsky G. V. (2020). Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells. Biomedicines, 8(5), 129.
Hartenian, E., Nandakumar, D., Lari, A., Ly, M., Tucker, J. M., & Glaunsinger, B. A. (2020). The molecular virology of coronaviruses. The Journal of biological chemistry, 295(37), 12910–12934.
Hess B., Bekker H., Berendsen H. J. C., & Fraaije J. G. E. M. (1997). LINCS: A linear constraint solver for molecular simulations. Journal of Computational Chemistry, 18(12), 1463–1472.
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271–280.e8.
Hooft, R. W., Vriend, G., Sander, C., & Abola, E. E. (1996). Errors in protein structures. Nature, 381(6580), 272.
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England), 395(10223), 497–506.
Hui, D. S., I Azhar, E., Madani, T. A., Ntoumi, F., Kock, R., Dar, O., Ippolito, G., Mchugh, T. D., Memish, Z. A., Drosten, C., Zumla, A., & Petersen, E. (2020). The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases, 91, 264–266.
Iser, B. P. M., Sliva, I., Raymundo, V. T., Poleto, M. B., Schuelter-Trevisol, F., & Bobinski, F. (2020). Suspected COVID-19 case definition: a narrative review of the most frequent signs and symptoms among confirmed cases. In SciELO Preprints.
Jaiswal, G., & Kumar, V. (2020). In-silico design of a potential inhibitor of SARS-CoV-2 S protein. PloS one, 15(10), e0240004.
Kaminski G. A., Friesner R. A., Tirado-Rives J., & Jorgensen W. L. (2001). Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. The Journal of Physical Chemistry B, 105(28), 6474–6487.
Khaerunnisa, S., Kurniawan, H., Awaluddin, R., Suhartati, S., & Soetjipto, S. (2020). Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study. Preprints 2020, 2020030226.
Khandia, R., Singhal, S., Alqahtani, T., Kamal, M. A., El-Shall, N. A., Nainu, F., Desingu, P. A., & Dhama, K. (2022). Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic. Environmental research, 209, 112816.
Kupferschmidt, K., & Vogel, G. (2021). How bad is Omicron? Some clues are emerging. Science (New York, N.Y.), 374(6573), 1304–1305.
Laskowski, R. A., Swindells, M. B. (2011). LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model. 51(10): 2778-86.
Lee, S., Lee, H. H., Shin, Y. S., Kang, H., & Cho, H. (2017). The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in RAW 264.7 cells. Arch Pharm Res.
Li, X., Geng, M., Peng, Y., Meng, L., & Lu, S. (2020). Molecular immune pathogenesis and diagnosis of COVID-19. Journal of pharmaceutical analysis, 10(2), 102–108.
Lyu, S. Y., Rhim, J. Y., & Park, W. B. (2005). Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro. Arch Pharm Res.
Maier, J. A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K. E., & Simmerling, C. (2015). ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput, 11(8), 3696-3713.
Marinho, T. O., Lucena, H. L. de, Sousa, A. P. de, da Silva, F. A, Medeiros, T. K. F. de, Souza, O. F., Alves, M. de S., Medeiros, M. A. A., Brito Junior, L. de, & Oliveira Filho, A. A. (2022). Antiviral activity of 1,8-cineole monoterpene: in silico study. Research, Society and Development, 11(4), e31011427363.
Mehrbod, P., Hudy, D., Shyntum, D., Markowski, J., Łos, M. J., & Ghavami, S. (2020). Quercetin as a Natural Therapeutic Candidate for the Treatment of Influenza Virus. Biomolecules, 11(1), 10.
Miyamoto S., & Kollman P. A. (1992). Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models. Journal of Computational Chemistry, 13(8), 952–962.
OLIVEIRA, Rafael Willian. (2020). Produtos Naturais no combate à Covid-19: uma revisão crítica de trabalhos publicados em 2020. Trabalho de Conclusão de Curso em Química Licenciatura – Universidade Federal de Uberlândia, Uberlândia.
Ospanov, M., León, F., Jenis, J., Khan, I. A., & Ibrahim, M. A. (2020). Challenges and future directions of potential natural products leads against 2019-nCoV outbreak. Current plant biology, 24, 100180.
Pan, X., Wang, H., Zhang, Y., Wang, X., Li, C., Ji, C., & Zhang, J. Z. (2022). AA-Score: a New Scoring Function Based on Amino Acid-Specific Interaction for Molecular Docking. Journal of Chemical Information and Modeling.
Pence, H. E. & Williams, A. (2010). ChemSpider: an online chemical information resource. J Chem Education, 87(11), 1123-1124.
Pontius, J., Richelle, J., & Wodak, S. J. (1996). Deviations from standard atomic volumes as a quality measure for protein crystal structures. Journal of molecular biology, 264(1), 121-136.
Rabaan, A. A., Al-Ahmed, S. H., Haque, S., Sah, R., Tiwari, R., Malik, Y. S., Dhama, K., Yatoo, M. I., Bonilla-Aldana, D. K., & Rodriguez-Morales, A. J. (2020). SARS-CoV-2, SARS-CoV, and MERS-COV: A comparative overview. Le infezioni in medicina, 28(2), 174–184.
Russo, M., Moccia, S., Spagnuolo, C., Tedesco, I., & Russo, G. L. (2020). Roles of flavonoids against coronavirus infection. Chemico-biological interactions, 328, 109211.
Saakre, M., Mathew, D., & Ravisankar, V. (2021). Perspectivas sobre drogas à base de flavonoides vegetais para o novo SARS-CoV-2. Revista da Universidade Beni-Suef de ciências básicas e aplicadas, 10(1), 21.
Schrödinger, L.L.C. O Sistema gráfico Molecular PyMOL, Versão 2.0 Schrödinger, LLC (2021).
Shakya, A., Chikhale, R. V., Bhat, H. R., Alasmary, F. A., Almutairi, T. M., Ghosh, S. K., Alhajri, H. M., Alissa, S. A., Nagar, S., & Islam, M. A. (2022). Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors. Molecular diversity, 26(1), 265–278.
Silva Neto, I. F., Ricardino, I. E. F., dos Santos, Í. T., de Lima, E. V. M., Souza, M. N. C., Marques, A. E. F., & Silva, M. R. (2020). Uma revisão da atividade antiviral do nim indiano e seu potencial frente ao novo coronavírus (SARS-CoV-2). Journal of Biology & Pharmacy and Agricultural Management, 17(1).
SILVA, Débora Lays. (2022). O uso de plantas medicinais em tempos de covid-19: uma revisão. (Trabalho de Conclusão de Curso – Monografia), Curso de Bacharelado em Farmácia, Centro de Educação e Saúde, Universidade Federal de Campina Grande, Cuité – Paraíba – Brasil.
Srinivasan, S., Cui, H., Gao, Z., Liu, M., Lu, S., Mkandawire, W., ... & Korkin, D. (2020). Structural genomics of SARS-CoV-2 indicates evolutionary conserved functional regions of viral proteins. Viruses, 12(4), 360.
Studer, G., Rempfer, C., Waterhouse, A. M., Gumienny, R., Haas, J., & Schwede, T. (2020). QMEANDisCo—distance constraints applied on model quality estimation. Bioinformatics, 36(6), 1765-1771.
Thakur, V., Bhola, S., Thakur, P., Patel, S., Kulshrestha, S., Ratho, R. K., & Kumar, P. (2022). SARS-CoV-2 waves and variants: understanding the causes and effect of the COVID-19 catastrophe. Infection, 50(2), 309-325.
Tian, W., Chen, C., Lei, X., Zhao, J., & Liang, J. (2018). CASTp 3.0: atlas computado de topografia superficial de proteínas. Pesquisa de ácidos nucleicos, 46(W1), W363-W367.
Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving docking speed and accuracy with a new scoring function, efficient optimization and multithreading. Journal of computational chemistry, 31(2), 455-461.
Wiederstein, M., & Sippl, M. J. (2007). ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic acids research, 35(Web Server issue), W407–W410.
World Health Organization (WHO) 2021. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern.
Wu, A., Peng, Y., Huang, B., Ding, X., Wang, X., Niu, P., Meng, J., Zhu, Z., Zhang, Z., Wang, J., Sheng, J., Quan, L., Xia, Z., Tan, W., Cheng, G., & Jiang, T. (2020). Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell host & microbe, 27(3), 325–328.
Yang, J., Zheng, Y., Gou, X., Pu, K., Chen, Z., Guo, Q., Ji, R., Wang, H., Wang, Y., & Zhou, Y. (2020). Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. International journal of infectious diseases - IJID, 94, 91–95.
Zarezade, V., Rezaei, H., Shakerinezhad, G., Safavi, A., Nazeri, Z., Veisi, A., ... & Shajirat, Z. (2021). The identification of novel inhibitors of human angiotensin-converting enzyme 2 and main protease of Sars-Cov-2: A combination of in silico methods for treatment of COVID-19. Journal of molecular structure, 1237, 130409.
Zhang, D., Hamdoun, S., Chen, R., Yang, L., Ip, C. K., Qu, Y., ... & Wong, V. K. W. (2021). Identification of natural compounds as SARS-CoV-2 entry inhibitors by molecular docking-based virtual screening with bio-layer interferometry. Pharmacological Research, 172, 105820.
Zheng J. (2020). SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat. International journal of biological sciences, 16(10), 1678–1685.
Zhu, Z., Lian, X., Su, X., Wu, W., Marraro, G. A., & Zeng, Y. (2020). From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respiratory research, 21(1), 1-14.
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