Document Type : Original Research Article

Authors

1 Department of Chemical Engineering, Faculty of Engineering, Universitas Muhammadiyah Surakarta, Surakarta, Indonesia

2 Biosensor Research Center, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Within this work, we have performed an in silico research for structural analysis of Favipiravir and its activity against COVID-19. To this aim, tautomers formations of Favipiravir have been first examined and found that four tautomeric structures could be considered as ligands obtained by density functional theory (DFT) calculations. The related protease and polymerase macromolecules to COVID-19 have been assigned as targets to examine the activity of ligands by Molecular Docking simulations. The results indicated that each of four ligands could interact with each of targets with different properties. F3 is the most stable tautomer and F1 is most active ligand against macromolecules. It has been found that the activity of ligands are more favorable for protease than polymerase target, but the ligand…target interacting complexes are not so much strong regarding low values of binding energies. Qualitative representations of ligand…target interactions also indicated different environments of interaction for complex formations. It is noted that further investigations are still required to examine the dominant activity of Favipiravir against COVID-19.

Graphical Abstract

Favipiravir: Structural Analysis and Activity against COVID-19

Keywords


1. Lipsitch M, Swerdlow DL, Finelli L. Defining the epidemiology of Covid-19 - studies needed. New Engl. J. Med. 2020.
2. Sun ML, Yang JM, Sun YP, Su GH. Inhibitors of RAS might be a good choice for the therapy of COVID-19 pneumonia. Chinese J. Tubercul. Respirator. Diseases 2020;43:E014.
3. Hatada R, Okuwaki K, Mochizuki Y, Fukuzawa K, Komeiji Y, Okiyama Y, Tanaka S. Fragment molecular orbital based interaction analyses on COVID-19 main protease-inhibitor N3 complex (PDB ID: 6LU7). ChemRxiv 2020.
4. Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y. Structure of Mpro from COVID-19 virus and discovery of its inhibitors. BioRxiv 2020.
5. Samadi Z, Mirzaei M, Hadipour NL, Khorami SA. Density functional calculations of oxygen, nitrogen and hydrogen electric field gradient and chemical shielding tensors to study hydrogen bonding properties of peptide group (OC–NH) in crystalline acetamide. Journal of Mol. Grap. Model. 2008;26:977-981.
6. Mirzaei M, Hadipour NL. Study of hydrogen bonds in 1-methyluracil by DFT calculations of oxygen, nitrogen, and hydrogen quadrupole coupling constants and isotropic chemical shifts. Chem. Phys. Lett. 2007;438:304-307.
7. Mirzaei M, Elmi F, Hadipour NL. A systematic investigation of hydrogen-bonding effects on the 17O, 14N, and 2H nuclear quadrupole resonance parameters of anhydrous and monohydrated cytosine crystalline structures: a density functional theory study. J. Phys. Chem. B 2006;110:10991-10996.
8. Behzadi H, Hadipour NL, Mirzaei M. A density functional study of 17O, 14N and 2H electric field gradient tensors in the real crystalline structure of α-glycine. Biophys. Chem. 2007;125:179-183.
9. Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antivir. Res. 2013;100:446-454.
10. Kiso M, Takahashi K, Sakai-Tagawa Y, Shinya K, Sakabe S, Le QM, Ozawa M, Furuta Y, Kawaoka Y. T-705 (Favipiravir) activity against lethal H5N1 influenza A viruses. Proc. Nat. Acad. Sci. 2010;107:882-887.
11. Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, Liao X, Gu Y, Cai Q, Yang Y, Shen C. Experimental treatment with Favipiravir for COVID-19: An open-label control study. Engineer. 2020.
12. Yaraghi A, Ozkendir OM, Mirzaei M. DFT studies of 5-fluorouracil tautomers on a silicon graphene nanosheet. Superlat.Microstruct. 2015;85:784-788.
13. Naderi E, Mirzaei M, Saghaie L, Khodarahmi G, Gulseren O. Relaxations of methylpyridinone tautomers at the C60 surfaces: DFT studies. Int. J. Nano Dimens. 2017;8:124-131.
14. Kouchaki A, Gülseren O, Hadipour N, Mirzaei M. Relaxations of fluorouracil tautomers by decorations of fullerene-like SiCs: DFT studies. Phys. Lett. A 2016;380:2160-2166.
16. Abyar Ghamsari P, Samadizadeh M, Mirzaei M. Cytidine derivatives as inhibitors of methyltransferase enzyme. Eurasian Chem. Commun. 2020;2:433-439.
16. Gilani AG, Taghvaei V, Rufchahi EM, Mirzaei M. Tautomerism, solvatochromism, preferential solvation, and density functional study of some heteroarylazo dyes. Journal of Mol. Liq. 2019;273:392-407
17. Soleimani M, Mirzaei M, Mofid MR, Khodarahmi G, Rahimpour SF. Lactoperoxidase inhibition by tautomeric propylthiouracils. Asian J. Green Chem. 2020;4:1-10.
18. Mirzaei M, Hadipour NL, Ahmadi K. Investigation of C–H… OC and N–H… OC hydrogen-bonding interactions in crystalline thymine by DFT calculations of O-17, N-14 and H-2 NQR parameters. Biophys. Chem. 2007;125:411-415.
19. Nazemi H, Mirzaei M, Jafari E. Antidepressant activity of curcumin by monoamine oxidase–A inhibition. J. Adv. Chem. B. 2019;1:3-9.
20. Carta A, Briguglio I, Piras S, Corona P, Ibba R, Laurini E, Fermeglia M, Pricl S, Desideri N, Atzori EM, La Colla P. A combined in silico/in vitro approach unveils common molecular requirements for efficient BVDV RdRp binding of linear aromatic N-polycyclic systems. Eur. J. Med. Chem. 2016;117:321-334.
21. Frisch MJ, Trucks GW, Schlegel HB, Scuseria, GE, Robb MA, Cheeseman JR, et al. Gaussian 09, Revision D.01. Gaussian, Inc., Wallingford CT, 2013.
22. Harismah K, Sadeghi M, Baniasadi R, Mirzaei M. Adsorption of vitamin C on a fullerene surface: DFT studies. J. Nanoanalyis. 2017;4:1-7.
23. Mokhtari A, Harismah K, Mirzaei M. Covalent addition of chitosan to graphene sheets: Density functional theory explorations of quadrupole coupling constants. Superlat. Microstruct. 2015;88:56-61.
24. Harismah K, Mirzaei M, Moradi R. DFT studies of single lithium adsorption on coronene. Z. Naturforsch. A 2018;73:685-691.
25. Harismah K, Mirzaei M, Sahebi H, Gülseren O, Rad AS. Chemically uracil–functionalized carbon and silicon carbide nanotubes: Computational studies. Mater. Chem. Phys. 2018;205:164-170.
26. Harismah K, Ozkendir OM, Mirzaei M. Explorations of crystalline effects on 4-(benzyloxy) benzaldehyde properties. Z. Naturforsch. A 2015;70:1013-1018.
27. K, Mirzaei M, Moradi R. DFT studies of single lithium adsorption on coronene. Z. Naturforsch. A 2018;73:685-691.
28. Mokhtari A, Harismah K, Mirzaei M. Covalent addition of chitosan to graphene sheets: Density functional theory explorations of quadrupole coupling constants. Superlat. Microstruct. 2015;88:56-61.
29. Kirchdoerfer RN, Ward AB. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nature Commun. 2019;10:1-9.
30. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009;30:2785-2791.
31. Esfahani AN, Mirzaei M. Flavonoid derivatives for monoamine oxidase–A inhibition. Adv. J. Chem. B. 2019;1:17-22.
32. Nabati M, Bodaghi-Namileh V. Design of novel tazarotene derivatives as potential antipsoriatic drugs: physicochemical properties study and molecular docking analysis of their binding to retinoic acid receptor family (RAR-alpha, RAR-beta and RAR-gamma). J. Med. Chem. Sci. 2020;3:162-175.
33. Nabati M, Bodaghi-Namileh V. Molecular Modeling of 3-(1, 3-Dioxoisoindolin-2-yl) benzyl Nitrate and its Molecular Docking Study with Phosphodiesterase-5 (PDE5). Adv. J. Chem. A 2020;3:58-69.