Evaluating the Molecular—Electronic Structure and the Antiviral Effect of Functionalized Heparin on Graphene Oxide Through Ab Initio Computer Simulations and Molecular Docking
Resumo
In antiviral studies, heparin is widely used against the SARS-CoV-2 virus. In this study, computer simulations were performed to understand the role of heparin in a possible blockade of the spike protein binding with the human cell receptor. Another molecule, graphene oxide (GO), was functionalized to interact and bind with heparin to achieve an increase in binding affinity with the spike protein. In the first stage. The electronic and chemical interaction between the molecules were analyzed through ab initio simulations by using Spanish Initiative for SIESTA (Electronic Simulations with Thousands of Atoms) Software. Next, we evaluated the interaction between molecules together and separately in the spike protein target through molecular docking simulations using AutoDock Vina Software. The results were relevant because GO functionalized with heparin exhibited an increase in affinity energy to the spike protein. This affinity indicated a possible increase in antiviral activity. This increase will be verified in the future through in vitro tests. Experimental tests on the synthesis and morphology of the material preliminarily indicate a good interaction between molecules and absorption of heparin by GO. This phenomenon confirmed the results of first principles simulations.
Palavras-chave:
coronavirus, drugs, pandemic
Referências
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Wang, D. et al.: An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics. J Infect Public Health. 13, 10, 1405–1414 (2020). https://doi.org/10.1016/j.jiph.2020.07.004.
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Wang, P. et al.: Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization. Cell Host Microbe. 29, 5, 747-751.e4 (2021). https://doi.org/10.1016/j.chom.2021.04.007.
Wang, X. et al.: Structural Insights into the Cofactor Role of Heparin/Heparan Sulfate in Binding between the SARS-CoV-2 Spike Protein and Host Angioten sin-Converting Enzyme II. J Chem Inf Model. 62, 3, 656–667 (2022). https://doi.org/10.1021/acs.jcim.1c01484.
Wang, Y. et al.: Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies. Nat Commun. 13, 1, 871 (2022). https://doi.org/10.1038/s41467-022-28528-w.
Chemcraft: Chemcraft - graphical software for visualization of quantum chemistry computationsy. https://www.chemcraftprog.com. Accessed 05 Dec 2022
Clausen, T.M. et al.: SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2. Cell. 183, 4, 1043-1057.e15 (2020). https://doi.org/10.1016/j.cell.2020.09.033.
Dacrory, S.: Antimicrobial Activity, DFT Calculations, and Molecular Docking of Dialdehyde Cellulose/Graphene Oxide Film Against Covid-19. J Polym Environ. 29, 7, 2248–2260 (2021). https://doi.org/10.1007/s10924-020-02039-5.
van Dijk, A.D.J., Bonvin, A.M.J.J.: Solvated docking: Introducing water into the modelling of biomolecular complexes. Bioinformatics. 22, 19, 2340–2347 (2006). https://doi.org/10.1093/bioinformatics/btl395.
Fukuda, M. et al.: Lethal Interactions of SARS-CoV-2 with Graphene Oxide: Implications for COVID-19 Treatment. ACS Appl Nano Mater. 4, 11, 11881–11887 (2021). https://doi.org/10.1021/acsanm.1c02446.
García, A. et al.: Siesta : Recent developments and applications. J Chem Phys. 152, 20, 204108 (2020). https://doi.org/10.1063/5.0005077.
Gobeil, S.M.-C. et al.: Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. Science (1979). 373, 6555, (2021). https://doi.org/10.1126/science.abi6226.
Gupta, I. et al.: Antiviral properties of select carbon nanostructures and their functionalized analogs. Mater Today Commun. 29, 102743 (2021). https://doi.org/10.1016/j.mtcomm.2021.102743.
Gupta, Y. et al.: Heparin: A simplistic repurposing to prevent SARS-CoV-2 transmission in light of its in-vitro nanomolar efficacy. Int J Biol Macromol. 183, 203–212 (2021). https://doi.org/10.1016/j.ijbiomac.2021.04.148.
HOPKINS, J.: Coronavirus Resource Center. https://coronavirus.jhu.edu/map.html
Hoseini-Ghahfarokhi, M. et al.: Applications of Graphene and Graphene Oxide in Smart Drug/Gene Delivery: Is the World Still Flat? Int J Nanomedicine. Volume 15, 9469–9496 (2020). https://doi.org/10.2147/IJN.S265876.
ICMAB: Instituto de Ciência de Materiais de Barcelona. https://departments.icmab.es/leem/siesta
Martins, M.O. et al.: Docking fundamentals for simulation in nanoscience. Disciplinarum Scientia - Ciências Naturais e Tecnológicas. 22, 3, 67–76 (2021). https://doi.org/10.37779/nt.v22i3.4106.
Mycroft-West, C.J. et al.: Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Do main with Heparin. Thromb Haemost. 120, 12, 1700–1715 (2020). https://doi.org/10.1055/s-0040-1721319.
Oliveira, A.M.L. et al.: Graphene Oxide Thin Films with Drug Delivery Function. Nanomaterials. 12, 7, 1149 (2022). https://doi.org/10.3390/nano12071149.
PDB Protein Data Bank: SARS-CoV-2 Omicron BA.4 variant spike. https://www.rcsb.org/structure/7XNQ https://doi.org/10.1038/s41586-022-04980-y.
Pedroza, L.S.: Desenvolvimento de novas aproximações para simulações ab initio. USP (2010).
Pubchem: Pubchem. https://pubchem.ncbi.nlm.nih.gov/compound/5288499. Accessed 02 Oct 2022
Rhazouani, A. et al.: Can the application of graphene oxide contribute to the fight against COVID-19? Antiviral activity, diagnosis and prevention. Current Re search in Pharmacology and Drug Discovery. 2, 100062 (2021). https://doi.org/10.1016/j.crphar.2021.100062.
dos Santos, A.F., et al.: In-Silico study of antivirals and non-antivirals for the treatment of SARS-COV-2. Disciplinarum Scientia - Ciências Naturais e Tecnológicas 23(2), 57–83 (2022). https://doi.org/10.37779/nt.v23i2.4200.
Schultz, J.V. et al.: Graphene oxide and flavonoids as potential inhibitors of the spike protein of SARS-CoV-2 variants and interaction between ligands: a parallel study of molecular docking and DFT. Struct Chem. (2023). https://doi.org/10.1007/s11224-023-02135-x.
Seabra, A.B. et al.: Nanotoxicity of Graphene and Graphene Oxide. Chem Res Toxicol. 27, 2, 159–168 (2014). https://doi.org/10.1021/tx400385x.
Seifi, T., Reza Kamali, A.: Antiviral performance of graphene-based materials with emphasis on COVID-19: A review. Med Drug Discov. 11, 100099 (2021). https://doi.org/10.1016/j.medidd.2021.100099.
Shafiee, A. et al.: Graphene and graphene oxide with anticancer applications: Challenges and future perspectives. MedComm (Beijing). 3, 1, (2022). https://doi.org/10.1002/mco2.118.
Tandon, R. et al.: Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives. J Virol. 95, 3, (2021). https://doi.org/10.1128/JVI.01987-20.
Trott, O., Olson, A.J.: AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. NA-NA (2009). https://doi.org/10.1002/jcc.21334.
Unal, M.A. et al.: Graphene Oxide Nanosheets Interact and Interfere with SARS‐CoV‐2 Surface Proteins and Cell Receptors to Inhibit Infectivity. Small. 17, 25, 2101483 (2021). https://doi.org/10.1002/smll.202101483.
Valdés-Tresanco, M.S. et al.: AMDock: a versatile graphical tool for assisting molecular docking with Autodock Vina and Autodock4. Biol Direct. 15, 1, 12 (2020). https://doi.org/10.1186/s13062-020-00267-2.
Wang, D. et al.: An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics. J Infect Public Health. 13, 10, 1405–1414 (2020). https://doi.org/10.1016/j.jiph.2020.07.004.
Wang, J. et al.: The Inhibition of SARS-CoV-2 3CL Mpro by Graphene and Its Derivatives from Molecular Dynamics Simulations. ACS Appl Mater Interfaces. 14, 1, 191–200 (2022). https://doi.org/10.1021/acsami.1c18104.
Wang, P. et al.: Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization. Cell Host Microbe. 29, 5, 747-751.e4 (2021). https://doi.org/10.1016/j.chom.2021.04.007.
Wang, X. et al.: Structural Insights into the Cofactor Role of Heparin/Heparan Sulfate in Binding between the SARS-CoV-2 Spike Protein and Host Angioten sin-Converting Enzyme II. J Chem Inf Model. 62, 3, 656–667 (2022). https://doi.org/10.1021/acs.jcim.1c01484.
Wang, Y. et al.: Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies. Nat Commun. 13, 1, 871 (2022). https://doi.org/10.1038/s41467-022-28528-w.
Publicado
13/06/2023
Como Citar
DOS SANTOS, André Flores; MARTINS, Mirkos Ortiz; TONEL, Mariana Zancan; FAGAN, Solange Binotto.
Evaluating the Molecular—Electronic Structure and the Antiviral Effect of Functionalized Heparin on Graphene Oxide Through Ab Initio Computer Simulations and Molecular Docking. In: SIMPÓSIO BRASILEIRO DE BIOINFORMÁTICA (BSB), 16. , 2023, Curitiba/PR.
Anais [...].
Porto Alegre: Sociedade Brasileira de Computação,
2023
.
p. 25-35.
ISSN 2316-1248.
