Estudio computacional sobre la reactividad y acoplamiento de aliina y astragalina como potenciales inhibidores de la proteasa principal del SARS-CoV-2

Wendolyne Lopez-Orozco; Luis Humberto Mendoza-Huizar; Giaan Arturo Álvarez-Romero; José de Jesús Martín Torres-Valencia

doi:10.29057/icbi.v10i20.9755

Wendolyne Lopez-Orozco Universidad Autónoma del Estado de Hidalgo https://orcid.org/0000-0003-4614-2234
Luis Humberto Mendoza-Huizar Universidad Autónoma del Estado de Hidalgo https://orcid.org/0000-0003-2373-4624
Giaan Arturo Álvarez-Romero Universidad Autónoma del Estado de Hidalgo https://orcid.org/0000-0002-9525-3937
José de Jesús Martín Torres-Valencia Universidad Autónoma del Estado de Hidalgo https://orcid.org/0000-0001-6426-7562

DOI: https://doi.org/10.29057/icbi.v10i20.9755

Palabras clave: Proteasa principal, Acoplamiento molecular, Semiempírico PM7, Astragalina, Aliina

Resumen

En el presente trabajo realizamos el estudio de reactividad para astragalina y aliina en el nivel de teoría semiempírico PM7 en la fase acuosa y empleando parámetros de reactividad global derivados de la Teoría de los funcionales de la densidad. Los resultados indican que aliina es mejor electrófilo, mientras que astragalina es una especie menos mutagénica. Se analizó también la capacidad de estos compuestos para acoplarse al proteasa MPro del SARS-COV-2 con la intención de determinar su potencial para inhibir la replicación de este virus. A partir del estudio de acoplamiento molecular Se evaluaron las afinidades de unión de los complejos y los valores de ΔG obtenidos para aliina y astragalina fueron -6.77 kcal mol^-1 y -8.52 kcal mol^-1, respectivamente. Aliina mostró interacciones con la proteasa principal (M^pro) del SARS-CoV-2 de tipo van der Waals con los residuos CYS145 y HSD164 que presentan la actividad catalítica M^pro del SARS-CoV-2. Por otro lado, astragalina interactúa con la proteasa mediante puentes de hidrógeno e interacciones tipo π-alquil con el residuo CYS145 y con HSD164 por interacción de enlaces de carbón. Estos resultados sugieren que los metabolitos aliina y astragalina interactúan con el bolsillo catalítico de la proteasa por lo que podrían actuar como inhibidores de la replicación del virus SARS-CoV-2.

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Alias, Norsyuhada, Siti Nur Akmal Ghazali, and Azzmer Azzar Abdul Hamid. 2020. “Molecular Docking and Dynamic Simulation of Astragalin Reveals Inhibitory Potential against Pancreatic Lipase.” International Journal of Allied Health Sciences 4(2): 1175–90.

Arodola, Olayide A., and Mahmoud E.S. Soliman. 2017. “Quantum Mechanics Implementation in Drug-Design Workflows: Does It Really Help?” Drug Design, Development and Therapy 11: 2551–64.

Ballón, Wendy, and Ricardo Grados. 2019. “Acomplamiento Molecular: Criterios Prácticos Para La Selección de Ligandos Biológicamente Activos e Identificación de Nuevos Blancos Terapéuticos.” Revista Con-Ciencia 7(2): 55–72.

Boehm, Erik et al. 2021. “Novel SARS-CoV-2 Variants: The Pandemics within the Pandemic.” Clinical Microbiology and Infection 27(8): 1109–17.

Boyd, Donald B. 2013. “Quantum Chemistry Program Exchange, Facilitator of Theoretical and Computational Chemistry in Pre-Internet History.” ACS Symposium Series 1122: 221–73. https://pubs.acs.org/doi/abs/10.1021/bk-2013-1122.ch008 (September 7, 2022).

Chattaraj, Pratim Kumar. 2009. “Chemical Reactivity Theory : A Density Functional View.” : 576. https://books.google.com/books/about/Chemical_Reactivity_Theory.html?hl=es&id=n8JBNvF_2KAC (December 16, 2021).

Chebaibi, Mohamed et al. 2021. “Medicinal Plants Against Coronavirus (SARS-COV-2) in Morocco Via Computational Virtual Screening Approach.” https://europepmc.org/article/PPR/PPR370491%0Ahttps://europepmc.org/article/ppr/ppr370491.

Firestone, Melanie J. et al. 2021. “First Identified Cases of SARS-CoV-2 Variant P.1 in the United States — Minnesota, January 2021.” Morbidity and Mortality Weekly Report 70(10): 346. /pmc/articles/PMC7951823/ (January 20, 2022).

Gázquez, José L. 2008. “Perspectives on the Density Functional Theory of Chemical Reactivity.” Journal of the Mexican Chemical Society 52(1): 3–10.

Graham, Mark S. et al. 2021. “Changes in Symptomatology, Reinfection, and Transmissibility Associated with the SARS-CoV-2 Variant B.1.1.7: An Ecological Study.” The Lancet Public Health 6(5): e335–45.

Jiang, Fang et al. 2020. “Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19).” Journal of General Internal Medicine 35(5): 1545–49.

Jin, Zhenming et al. 2020. “Structure of M pro from SARS-CoV-2 and Discovery of Its Inhibitors.” (February).

Kannan, Saathvik R. et al. 2021. “Evolutionary Analysis of the Delta and Delta Plus Variants of the SARS-CoV-2 Viruses.” Journal of Autoimmunity 124: 102715.

Klamt, Andreas. 2011. “The COSMO and COSMO-RS Solvation Models.” Wiley Interdisciplinary Reviews: Computational Molecular Science 1(5): 699–709.

Koopmans, T., Koopmans, and T. 1934. “Über Die Zuordnung von Wellenfunktionen Und Eigenwerten Zu Den Einzelnen Elektronen Eines Atoms.” Phy 1(1): 104–13. https://ui.adsabs.harvard.edu/abs/1934Phy.....1..104K/abstract (December 1, 2022).

Lam-Hine, Tracy et al. 2021. “Outbreak Associated with SARS-CoV-2 B.1.617.2 (Delta) Variant in an Elementary School — Marin County, California, May–June 2021.” Morbidity and Mortality Weekly Report 70(35): 1214. /pmc/articles/PMC8422870/ (January 20, 2022).

Lespade, Laure, and Sylvie Bercion. 2012. “Theoretical Investigation of the Effect of Sugar Substitution on the Antioxidant Properties of Flavonoids.” Free Radical Research 46(3): 346–58.

Macías-Villamizar, Víctor, and Roxana González-Ascanio. 2019. “Plantas de Santa Marta Con Posible Actividad Biológica Antimicrobiana.” Duazary 16(2): 414–39.

MacKerell, Alexander D., Nilesh Banavali, and Nicolas Foloppe. 2000. “Development and Current Status of the CHARMM Force Field for Nucleic Acids.” Biopolymers 56(4): 257–65.

Mehdi, Anwar, Widad M K Al-ani, and Ayad Raoof. 2018. “ISOLATION OF ASTRAGALIN FROM IRAQI CHENOPODIUM ALBUM.” 11(12).

Nikolić, Vesna D. et al. 2012. “The Synthesis and Structure Characterization of Deoxyalliin and Alliin.” Savremene tehnologije / Advanced Technologies 1(1): 38–46. http://www.tf.ni.ac.rs/casopis/sveska1/savremene1.php.

Parr, Robert G., Robert A. Donnelly, Mel Levy, and William E. Palke. 1977. “Electronegativity: The Density Functional Viewpoint.” The Journal of Chemical Physics 68(8): 3801–7.

Parr, Robert G., and Ralph G. Pearson. 1983. “Absolute Hardness: Companion Parameter to Absolute Electronegativity.” Journal of the American Chemical Society 105(26): 7512–16.

Parr, Robert G., László V. Szentpály, and Shubin Liu. 1999. “Electrophilicity Index.” Journal of the American Chemical Society 121(9): 1922–24.

Pearson, Ralph G. 1987. “Recent Advances in the Concept of Hard and Soft Acids and Bases.” Journal of Chemical Education 64(7): 561–67.

Peramo-Álvarez, Francisco Pablo, Miguel Ángel López-Zúñiga, and Miguel Ángel López-Ruz. 2021. “Medical Sequels of COVID-19.” Medicina Clinica 157(8): 388–94.

Riaz, Ammara et al. 2018. “Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities.” Advances in Pharmacological Sciences 2018.

Roy, Nabarun, PA Nazeem, and PS Abida. 2017. “Comparative Docking Studies to Prove the Accuracy of Computational Tools for Recognizing the Inhibitory Action of Garlic (Allium Sativum L.) on Diabetes.” International Journal of Chemical Studies 5(July): 342–45.

Spera, Marcelle B.M. et al. 2011. “Palladium(II) Complex with S-Allyl-l-Cysteine: New Solid-State NMR Spectroscopic Measurements, Molecular Modeling and Antibacterial Assays.” Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 78(1): 313–18. http://dx.doi.org/10.1016/j.saa.2010.10.012.

Stewart, James J.P. 2013. “Optimization of Parameters for Semiempirical Methods VI: More Modifications to the NDDO Approximations and Re-Optimization of Parameters.” Journal of Molecular Modeling 19(1): 1–32.

“SwissDock - The Online Docking Web Server of the Swiss Institute of Bioinformatics - Home.” http://www.swissdock.ch/ (January 20, 2022).

Team, CDC COVID-19 Response. 2021. “SARS-CoV-2 B.1.1.529 (Omicron) Variant — United States, December 1–8, 2021.” Morbidity and Mortality Weekly Report 70(50): 1731. /pmc/articles/PMC8675659/ (January 20, 2022).

Tekin, Emine Deniz. 2010. “INVESTIGATION OF BIOLOGICALLY IMPORTANT SMALL MOLECULES: QUANTUM CHEMICAL AND MOLECULAR DYNAMICS CALCULATIONS.”

Tu, Yung Fang et al. 2020. “A Review of Sars-Cov-2 and the Ongoing Clinical Trials.” International Journal of Molecular Sciences 21(7).

Valencia, Damian N. 2020. “Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2.” Cureus 12(3). /pmc/articles/PMC7179986/ (December 16, 2021).

Vicidomini, Caterina, Valentina Roviello, and Giovanni N. Roviello. 2021. “In Silico Investigation on the Interaction of Chiral Phytochemicals from Opuntia Ficus-Indica with Sars-Cov-2 Mpro.” Symmetry 13(6).

Wondrousch, Dominik et al. 2010. “Local Electrophilicity Predicts the Toxicity-Relevant Reactivity of Michael Acceptors.” Journal of Physical Chemistry Letters 1(10): 1605–10.