Penambatan Molekul Senyawa Aktif Spirulina platensis sebagai Inhibitor TMPRSS2 untuk Mencegah Infeksi SARS-COV-2 Molecular Docking of Active Compound of Spirulina platensis as TMPRSS2 Inhibitor to Prevent the SARS-COV-2 Infection
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Accepted
22 July 2022
Published
10 August 2022
Keywords:
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COVID-19, Molecular docking, Spirulina platensis, SARS-COV-2, TMPRSS2
Abstract
Spirulina platensis is a blue green algae (Cyanophyta) species that consumed as a healthy food and as a source of various types of nutritions that needed by the human body. The compounds that isolated from the microalgae has been reported as effective inhibitors against several types of viruses. COVID-19 is a disease that caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In mechanism, spike protein SARS-CoV-2 is activated by TMPRSS2 to enter host cells. Thus, inhibiting TMPRSS2 activity can be prevent the SARS-COV-2 infection. This study aims to analyze the potential of the active compound of the extracts of S. platensis as TMPRSS2 inhibitor to prevent the SARS-COV-2 infection that expected to reduce the severity of the COVID-19. This study using molecular docking study based on the affinity energy (ΔG) and inhibition constant (Ki). The potential active compound also compared to natural ligands and nafamostat. Molecular docking was conducted on 45 of 108 active compounds of S. platensis with TMPRSS2 protein. Molecular docking results indicate that quercitrin has the potential as a TMPRSS2 inhibitor due to its most negative ΔG by -7.40 kcal/mol and inhibition constant by 3.77 M. The quercitrin also can bind to 2 residues from the active side of TMPRSS2 than natural ligands and nafamostat that only bind to 1 residue of the active side of TMPRSS2.
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Dhanik A, McMurray JS, Kavraki LE. 2013. DINC: a new AutoDock-based protocol for docking large ligands. BMC structural biology. 13(1):1–14.
Elshouny WAE-F, El-Sheekh MM, Sabae SZ, Khalil MA, Badr HM. 2021. Antimicrobial activity of Spirulina platensis against aquatic bacterial isolates. Journal of Microbiology, Biotechnology and Food Sciences. 2021:1203–1208.
Fraser BJ, Beldar S, Seitova A, Hutchinson A, Mannar D, Li Y, Kwon D, Tan R, Wilson RP, Leopold K. 2021. Structure, activity and inhibition of human TMPRSS2, a protease implicated in SARS-CoV-2 activation. BioRxiv.
Gabr GA, El-Sayed SM, Hikal MS. 2020. Antioxidant activities of phycocyanin: A bioactive compound from Spirulina platensis. J. Pharm. Res. Int. 32:73–85.
Han SJ, Kim HS, Kim KI, Whang SM, Hong KS, Lee WK, Lee SH. 2011. Use of nafamostat mesilate as an anticoagulant during extracorporeal membrane oxygenation. Journal of Korean Medical Science. 26(7):945–950.
Hempel T, Raich L, Olsson S, Azouz NP, Klingler AM, Hoffmann M, Pöhlmann S, Rothenberg ME, Noé F. 2021. Molecular mechanism of inhibiting the SARS-CoV-2 cell entry facilitator TMPRSS2 with camostat and nafamostat. Chemical Science. 12(3):983–992.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N-H, Nitsche A. 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.
Joseph J, Ajay A, Das V, Raj VS. 2020. Green tea and Spirulina extracts inhibit SARS, MERS, and SARS-2 spike pseudotyped virus entry in vitro. Current Pharmaceutical Biotechnolology.
Kalyaanamoorthy S, Barakat KH. 2018. Development of safe drugs: the hERG challenge. Medicinal Research Reviews. 38(2):525–555.
KEMENKES RI. 2021. BUKU SAKU VAKSINASI COVID-19. EDISI PERTAMA (MEI 2021). Kementerian Kesehatan RI Direktorat Jenderal Pencegahan dan Pengendalian Penyakit.
Ko M, Jeon S, Ryu W-S, Kim S. 2020. Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells: Nafamostat is the most potent antiviral drug candidate. BioRxiv.
Kumar V, Bhatnagar A, Srivastava J. 2011. Antibacterial activity of crude extracts of Spirulina platensis and its structural elucidation of bioactive compound. Journal of Medicinal Plants Research. 5(32):7043–7048.
Lamothe SM, Guo J, Li W, Yang T, Zhang S. 2016. The human ether-a-go-go-related gene (hERG) potassium channel represents an unusual target for protease-mediated damage. Journal of Biological Chemistry. 291(39):20387–20401.
Li X, Chen L, Cheng F, Wu Z, Bian H, Xu C, Li W, Liu G, Shen X, Tang Y. 2014. In silico prediction of chemical acute oral toxicity using multi-classification methods. Journal of Chemical Information and Modeling. 54(4):1061–1069.
Li X, Du Z, Wang J, Wu Z, Li W, Liu G, Shen X, Tang Y. 2015. In silico estimation of chemical carcinogenicity with binary and ternary classification methods. Molecular Informatics. 34(4):228–235.
Lipinski CA. 2004. Lead-and drug-like compounds: the rule-of-five revolution. Drug discovery today: Technologies. 1(4):337–341.
Lovell SC, Davis IW, Arendall III WB, De Bakker PI, Word JM, Prisant MG, Richardson JS, Richardson DC. 2003. Structure validation by Cα geometry: ϕ, ψ and Cβ deviation. Proteins: Structure, Function, and Bioinformatics. 50(3):437–450.
Lupatini AL, Colla LM, Canan C, Colla E. 2017. Potential application of microalga Spirulina platensis as a protein source. Journal of the Science of Food and Agriculture. 97(3):724–732.
Ozdemir G, Ulku Karabay N, Dalay MC, Pazarbasi B. 2004. Antibacterial activity of volatile component and various extracts of Spirulina platensis. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 18(9):754–757.
Perrin MJ, Subbiah RN, Vandenberg JI, Hill AP. 2008. Human ether-a-go-go related gene (hERG) K+ channels: function and dysfunction. Progress in Biophysics and Molecular Biology. 98(2–3):137–148.
Roden DM. 2004. Drug-induced prolongation of the QT interval. New England Journal of Medicine. 350(10):1013–1022.
Shrimp JH, Kales SC, Sanderson PE, Simeonov A, Shen M, Hall MD. 2020. An enzymatic TMPRSS2 assay for assessment of clinical candidates and discovery of inhibitors as potential treatment of COVID-19. ACS Pharmacology & Translational Science. 3(5):997–1007.
Sommella E, Conte GM, Salviati E, Pepe G, Bertamino A, Ostacolo C, Sansone F, Prete FD, Aquino RP, Campiglia P. 2018. Fast profiling of natural pigments in different spirulina (arthrospira platensis) dietary supplements by DI-FT-ICR and evaluation of their antioxidant potential by pre-column DPPH-UHPLC assay. Molecules. 23(5):1152.
Trott O, Olson AJ. 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry. 31(2):455–461.
Umamaheswari M, Madeswaran A, Asokkumar K. 2013. Virtual screening analysis and in-vitro xanthine oxidase inhibitory activity of some commercially available flavonoids. Iranian Journal of Pharmaceutical Research: IJPR. 12(3):317.
Verdonk ML, Chessari G, Cole JC, Hartshorn MJ, Murray CW, Nissink JWM, Taylor RD, Taylor R. 2005. Modeling water molecules in protein− ligand docking using GOLD. Journal of Medicinal Chemistry. 48(20):6504–6515.
Walum E. 1998. Acute oral toxicity. Environmental Health Perspectives. 106(suppl 2):497–503.
World Health Organization. 2020a. Tatalaksana klinis infeksi saluran pernapasan akut berat (SARI) suspek penyakit COVID-19. World Health Organization. 4:1–25.
World Health Organization. 2020b. Novel Coronavirus (2019-nCoV). Situation Report–22, Data as reported by 11 February 2020.
Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu Y, Li M, Li X. 2020. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B. 10(5):766–788.
Authors
KalontongP. K., SafithriM., & TarmanK. (2022). Penambatan Molekul Senyawa Aktif Spirulina platensis sebagai Inhibitor TMPRSS2 untuk Mencegah Infeksi SARS-COV-2: Molecular Docking of Active Compound of Spirulina platensis as TMPRSS2 Inhibitor to Prevent the SARS-COV-2 Infection. Jurnal Pengolahan Hasil Perikanan Indonesia, 25(2), 253-267. https://doi.org/10.17844/jphpi.v25i2.40645
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