European Journal of Biology

SUBMITINFORMATION
EnglishTürkçe

Research Article


DOI :10.26650/EurJBiol.2024.1389569   IUP :10.26650/EurJBiol.2024.1389569    Full Text (PDF)

In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes

Gözde Yılmaz, Sefa Çelik, Ayşen Erbölükbaş Özel, Sevim Akyüz

Objective: Short peptides play a significant role in exploring drugs with higher selectivity and fewer side effects in cancer and COVID-19 therapies. This study evaluated the anticancer and anti-COVID-19 activities of Glu-Arg-Gln (ERQ) tripeptide for the first time. To discover the potentiality of the tripeptide as an anticancer and as a SARS-CoV-2 inhibitor, molecular docking analysis of ERQ tripeptide with DNA (PDB ID: 1BNA) and a variety of SARS-CoV-2 enzymes, namely. Main protease (PDB IDs: 6M03, 6LU7) and Spike glycoprotein (PDB ID: 6VXX) were performed.

Materials and Methods: To determine the binding efficiency of ERQ to target DNA and proteins, molecular docking processes were carried out using the Autodock Vina program. The sorts of bonds and interacting residues in ERQ/DNA and ERQ/protein complexes were determined.

Results: Molecular docking simulations of ERQ tripeptide against 1BNA, 6M03, 6LU7, and 6VXX were performed, and the interactions between the docked ligand and target residues were determined. The binding mechanisms of ERQ with the receptors were clarified. The binding affinities of ERQ towards the targets were predicted to be between -6.3 and -6.7 kcal/mol. ERQ showed the highest binding affinity to Spike glycoprotein (6VXX), with an estimated binding energy of -6.7 kcal/mol.

Conclusion: Molecular docking simulations revealed the potential of ERQ tripeptide as an anticancer and anti-COVID-19 agent. High binding affinity against 1BNA (-6.4 kcal/mol), 6M03 (-6.3 kcal/mol), 6LU7 (-6.6 kcal/mol), and 6VXX (-6.7 kcal/mol) indicated that ERQ could be an excellent new natural therapy for the treatment of cancer and COVID-19.

Keywords: In silico, Molecular docking, Glu-Arg-Gln, ERQ, Tripeptide

PDF View

References

  • Nikfar Z, Shariatinia Z. The RGD tripeptide anticancer drug car-rier: DFT computations and molecular dynamics simulations. J Mol Liq. 2019;281:565-583. google scholar
  • Sun A, Shoji M, Lu YJ, Liotta DC, Snyder, JP. Synthesis of EF24-tripeptide chloromethyl ketone: A novel curcumin-related anticancer drug delivery system. J Med Chem. 2006;49(11):3153-3158. google scholar
  • Ali H, Jabeen A, Maharjan, R, et al. Furan-conjugated tripep-tides as potent antitumor drugs. Biomolecules. 2020;10(12):1684. doi:10.3390/biom10121684 google scholar
  • Lau JL, Dunn MK. Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg Med Chem. 2018;26(10):2700-2707. google scholar
  • Ye N, Ding Y, Wild C, Shen Q, Zhou J. Small molecule inhibitors targeting activator protein 1 (AP-1). J Med Chem. 2014;57(16):6930-6948. google scholar
  • Kumar A, Kothari J, Lokhande KB, Seethamma TN, Venkateswara Swamy K, Sharma NK. Novel antiproliferative tripeptides inhibit AP-1 transcriptional complex. Int J Pept Res Ther. 2021;27(4):2163-2182. google scholar
  • Fan J, Fu A, Zhang L. Progress in molecular docking. Quant Biol. 2019;7(2):83-89. google scholar
  • Pagadala NS, Syed K, Tuszynski J. Software for molecular dock-ing: A review. Biophys Rev. 2017;9(2):91-102. google scholar
  • Gilad Y, Senderowitz H. Docking studies on DNA intercalators. J Chem Inf Model. 2014;54(1):96-107. google scholar
  • Celik S, Vagifli F, Akyuz S, et al. Synthesis, vibrational spec-troscopic investigation, molecular docking, antibacterial and an-timicrobial studies of a new anthraquinone derivative compound. Spectrosc Lett. 2022;55(4):259-277. google scholar
  • Protein Data Bank website. http://www.rcsb.org/pdb. Accessed November 09, 2023. google scholar
  • Halgren TA. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J Comput Chem. 1996;17(5-6):490-519. google scholar
  • Shao Y, Molnar LF, Jung Y, et al. Advances in methods and algorithms in a modern quantum chemistry program package. Phys Chem Chem Phys. 2006;8(27):3172-3191. google scholar
  • Trott O, Olson AJ. Autodock vina: Improving the speed and accu-racy of docking with a new scoring function, efficient optimiza-tion, and multithreading. J Comput Chem. 2010;31:455-461. google scholar
  • Drew HR, Wing RM, Takano T, et al. Structure of a B-DNA do-decamer: Conformation and dynamics. Proc Natl Acad Sci USA. 1981;78(4): 2179-2183. google scholar
  • Zhao Y, Zhu Y, Liu X, et al. Structural basis for repli-case polyprotein cleavage and substrate specificity of main protease from SARS-CoV-2. Proc Natl Acad Sci USA. 2022;119(16):e2117142119. doi:10.1073/pnas.2117142119 google scholar
  • Jin Z, Du X, Xu Y, et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;582(7811):289-293. google scholar
  • Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181(2):281-292. google scholar
  • Jurcik A, Bednar D, Byska J, et al. Caver analyst 2.0: Anal-ysis and visualization of channels and tunnels in protein structures and molecular dynamics trajectories. Bioinformatics. 2018;34(20):3586-3588. google scholar
  • Demirag AD, Çelik S, Akyuz S, Ozel A. Molecular docking anal-ysis of used drugs for the treatment of cancer. Süleyman Demirel University J Nat App Sci. 2021;25(3):539-547. google scholar
  • Sagaama A, Brandan SA, Issa TB, Issaoui N. Searching po-tential antiviral candidates for the treatment of the 2019 novel coronavirus based on DFT calculations and molecular docking. Heliyon. 2020;6(8): e04640. doi:10.1016/j.heliyon.2020.e04640 google scholar
  • Arifa Begum SK, Begum S, Bandari P, Swapna BS, Reddemma M. Tetrandrine, an effective inhibitor of COVID-19 main protease (Mpro); Insights from molecular docking and dynamics simula-tions. Int J Pharm Investig. 2023;13(4):845-851. google scholar
  • Celik S, Yilmaz G, Akyuz S, Ozel AE. Shedding light into the bio-logical activity of aminopterin, via molecular structural, docking, and molecular dynamics analyses. J Biomol Struct Dyn. 2023;1-22. doi:10.1080/07391102.2023.2245493 google scholar
  • Liu X, Wang XJ. Potential inhibitors against 2019-nCoV coron-avirus M protease from clinically approved medicines. J Genet Genomics. 2020;47(2):119-121. google scholar
  • Özdemir M, Köksoy B, Ceyhan D, Bulut M, Yalcin B. In silico, 6LU7 protein inhibition using dihydroxy-3-phenyl coumarin derivatives for SARS-CoV-2. J Turk Chem Soc Sect A Chem. 2020;7(3):691-712. google scholar
  • Hatada R, Okuwaki K, Mochizuki Y, et al. Fragment molecular orbital based interaction analyses on COVID-19 main protease-inhibitor n3 complex (PDB ID:6LU7). J Chem Inf Model. 2020;60(7):3593-3602. google scholar
  • Celik S, Akyuz S, Ozel AE. Vibrational spectroscopic characterization and structural investigations of cepharan-thine, a natural alkaloid. J Mol Struct. 2022;1258:132693. https://doi.org/10.1016/j.molstruc.2022.132693 google scholar
  • Holanda VN, Lima EMDA, Silva WVD, et al. Identification of 1, 2, 3-triazole-phthalimide derivatives as potential drugs against COVID-19: A virtual screening, docking and molecular dynamic study. J Biomol Struct Dyn. 2022;40(12):5462-5480. google scholar
  • Joshi A, Sharma V, Singh J, Kaushik V. Chemi-informatic ap-proach to investigate putative pharmacoactive agents of plant ori-gin to eradicate COVID-19. Coronaviruses. 2022;3(3):40-54. google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Yılmaz, G., Çelik, S., Özel, A.E., & Akyüz, S. (2024). In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes. European Journal of Biology, 83(1), 34-41. https://doi.org/10.26650/EurJBiol.2024.1389569


AMA

Yılmaz G, Çelik S, Özel A E, Akyüz S. In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes. European Journal of Biology. 2024;83(1):34-41. https://doi.org/10.26650/EurJBiol.2024.1389569


ABNT

Yılmaz, G.; Çelik, S.; Özel, A.E.; Akyüz, S. In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes. European Journal of Biology, [Publisher Location], v. 83, n. 1, p. 34-41, 2024.


Chicago: Author-Date Style

Yılmaz, Gözde, and Sefa Çelik and Ayşen Erbölükbaş Özel and Sevim Akyüz. 2024. “In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes.” European Journal of Biology 83, no. 1: 34-41. https://doi.org/10.26650/EurJBiol.2024.1389569


Chicago: Humanities Style

Yılmaz, Gözde, and Sefa Çelik and Ayşen Erbölükbaş Özel and Sevim Akyüz. “In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes.” European Journal of Biology 83, no. 1 (Nov. 2024): 34-41. https://doi.org/10.26650/EurJBiol.2024.1389569


Harvard: Australian Style

Yılmaz, G & Çelik, S & Özel, AE & Akyüz, S 2024, 'In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes', European Journal of Biology, vol. 83, no. 1, pp. 34-41, viewed 22 Nov. 2024, https://doi.org/10.26650/EurJBiol.2024.1389569


Harvard: Author-Date Style

Yılmaz, G. and Çelik, S. and Özel, A.E. and Akyüz, S. (2024) ‘In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes’, European Journal of Biology, 83(1), pp. 34-41. https://doi.org/10.26650/EurJBiol.2024.1389569 (22 Nov. 2024).


MLA

Yılmaz, Gözde, and Sefa Çelik and Ayşen Erbölükbaş Özel and Sevim Akyüz. “In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes.” European Journal of Biology, vol. 83, no. 1, 2024, pp. 34-41. [Database Container], https://doi.org/10.26650/EurJBiol.2024.1389569


Vancouver

Yılmaz G, Çelik S, Özel AE, Akyüz S. In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes. European Journal of Biology [Internet]. 22 Nov. 2024 [cited 22 Nov. 2024];83(1):34-41. Available from: https://doi.org/10.26650/EurJBiol.2024.1389569 doi: 10.26650/EurJBiol.2024.1389569


ISNAD

Yılmaz, Gözde - Çelik, Sefa - Özel, AyşenErbölükbaş - Akyüz, Sevim. “In Silico Evaluation of ERQ Bioactive Tripeptide as an Anticancer Agent and an Inhibitor of SARS-CoV-2 Enzymes”. European Journal of Biology 83/1 (Nov. 2024): 34-41. https://doi.org/10.26650/EurJBiol.2024.1389569



TIMELINE


Submitted11.11.2023
Accepted09.12.2023
Published Online14.02.2024

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.