Theoretical investigation of the derivatives of favipiravir (T-705) as potential drugs for Ebola virus
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Lydia Rhyman
, Mahir Tursun
Abstract
Density functional theory (DFT) method was used to compute the structural and vibrational parameters of favipiravir (T-705) in the gas phase. The functional used was B3LYP in conjuction with the 6–311++G(d,p) basis set. We also computed these parameters for unsubstituted T-705 and derivatives of T-705 by substituting fluorine by chlorine, bromine and the cyanide group. There is a good comparison between the computed and experimental parameters for T-705 and therefore, the predicted data should be reliable for the other compounds for which experimental data is not available. We extended our DFT study to include molecular docking involving the Ebola virus viral protein 35 (VP35). The docking results indicate that the T-705 and its chlorine and bromine analogues have comparable free energy of binding with VP35.
Graphical Abstract:

Acknowledgements
The authors acknowledge the facilities from their respective universities.
References
[1] Centers for disease controls and prevention. 2014. Outbreaks chronology: Ebola haemorrhagic fever. Available at: http://www.cdc.gov/vhf/ebola/. Accessed: Jan 2016.Suche in Google Scholar
[2] Hayden E. The Ebola questions: scientists know a lot about the virus that causes Ebola — but there are many puzzles that they have yet to solve. Nature. 2014;514:554–7.10.1038/514554aSuche in Google Scholar PubMed
[3] Baize S, Pannetier D, Oestereich L, et al. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 2014;371:1418–25.10.1056/NEJMoa1404505Suche in Google Scholar PubMed
[4] http://www.who.int/mediacentre/news/releases/2016/ebola-zero-liberia/en/. Accessed: Dec 2016.Suche in Google Scholar
[5] Ippolito G, Puro V, Piselli P. Ebola in West Africa: who pays for what in the outbreak? New Microbiol. 2015;38:1–3.Suche in Google Scholar PubMed
[6] The Economist. Ebola’s legacy after the passing, The virus will have a long-lasting impact on already poor countries. 2015. Available at: http://www.economist.com/news/middle-east-and-africa/21637391-virus-will-have-long-lasting-impact-already-poor-countries-after. Accessed: Dec. 2016.Suche in Google Scholar
[7] Zhang Y, Li H, Cheng A. Ebola haemorrhagic fever. In: Li H, editor. Radiology of infectious diseases: volume 1, Chapter 13. Dordrecht, Heidelberg, New York, London: Springer Science+Business Media Dordrecht and People’s Medical Publishing House, 2015.Suche in Google Scholar
[8] Judson S, Prescott J, Munster V. Understanding Ebola virus transmission. Viruses. 2015;7:511–21.10.3390/v7020511Suche in Google Scholar PubMed PubMed Central
[9] Mendoza EJ, Qiu X, Kobinger GP. Progression of Ebola therapeutics during the 2014–2015 outbreak. Trends Mol Med. 2016;22:164–73.10.1016/j.molmed.2015.12.005Suche in Google Scholar PubMed
[10] Kaushik A, Tiwari S, Jayant RD, et al. Towards detection and diagnosis of Ebola virus disease at point-of-care. Biosens Bioelectron. 2016;75:254–72.10.1016/j.bios.2015.08.040Suche in Google Scholar PubMed PubMed Central
[11] http://www.who.int/medicines/emp_ebola_q_as/en/. Accessed: Dec 2016.Suche in Google Scholar
[12] Buttler D. Ebola drug trials set to begin amid crisis. Nature. 2014;513:156.10.1038/513013aSuche in Google Scholar PubMed
[13] Furuta Y, Takahashi K, Shiraki K, et al. T-705 (Favipiravir) and related compounds: novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res. 2009;82:95–102.10.1016/j.antiviral.2009.02.198Suche in Google Scholar PubMed PubMed Central
[14] Furuta Y, Gowen BB, Takahashi K, et al. Favipiravir (T-705) a novel viral RNA polymerase inhibitor. Antiviral Res. 2013;100:446–54.10.1016/j.antiviral.2013.09.015Suche in Google Scholar PubMed PubMed Central
[15] Furuta Y, Takahashi K. Inventors; Toyama Chemical Co., Ltd., assignee. Nitrogenous heterocyclic carboxamide derivatives or salts thereof and antiviral agents containing both. CA2339272A1. 2 Mar 2000.Suche in Google Scholar
[16] Shi F, Zongtao L, Kong, L, et al. Synthesis and crystal structure of 6-fluoro-3-hydroxypyrazine-2-carboxamide. Drug Discov Ther. 2014;8:117–20.10.5582/ddt.2014.01028Suche in Google Scholar PubMed
[17] De Clercq E. Antivirals: past, present and future. Biochem Pharmocol. 2013;85:727–44.10.1016/j.bcp.2012.12.011Suche in Google Scholar PubMed
[18] De Clercq E. Dancing with chemical formulae of antivirals: A personal account. Biochem Pharmocol. 2013;86:711–25.10.1016/j.bcp.2013.07.012Suche in Google Scholar
[19] De Clercq E. Dancing with chemical formulae of antivirals: A panoramic view (part 2). Biochem Pharmocol. 2013;86:1397–410.10.1016/j.bcp.2013.09.010Suche in Google Scholar
[20] Hernandes MZ, Cavalcanti SM, Moreira DR, et al. Halogen atoms in the modern medicinal chemistry: hints for the drug design. Curr Drug Targets. 2010;11:303–14.10.2174/138945010790711996Suche in Google Scholar PubMed
[21] Kharkar PS, Ramasami P, Choong YS, et al. Discovery of anti-Ebola drugs: a computational drug repositioning case study. RSC Adv. 2016;6:26329–40.10.1039/C6RA01704ESuche in Google Scholar
[22] Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 09, revision D.01. Wallingford CT: Gaussian, Inc, 2009.Suche in Google Scholar
[23] Dooley R, Milfeld K, Guiang C, Pamidighantam S, Allen G. From proposal to production: lesson learned developing the computational chemistry grid cyberinfrastructure. J Grid Comput. 2006;4:195–208.10.1007/s10723-006-9043-7Suche in Google Scholar
[24] Milfeld K, Guiang C, Pamidighantam S, Giuliani J. Proceedings of the 2005 Linux Clusters: The HPC Revolution, NCSA University of Illinois, CHPC University of New Mexico and IBM, 2005.Suche in Google Scholar
[25] Dooley R, Allen G, Pamidighantam S. Proceedings of the 13th Annual Mardi Gras Conference, CCT. Baton Rouge, LA: Louisiana State University, 2005:83.Suche in Google Scholar
[26] Brown CS, Lee MS, Leung DW, et al. In silico derived small molecules bind the filovirus VP35 protein and inhibit its polymerase cofactor activity. J Mol Biol. 2014;426:2045–58.10.1016/j.jmb.2014.01.010Suche in Google Scholar PubMed
[27] Morris GM, Goodsell DS, Halliday RS, et al. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 1998;19:1639–62.10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-BSuche in Google Scholar
[28] HyperChem(TM) Professional 7.51, Hypercube, Inc., 1115 NW 4th Street, Gainesville, Florida 32601, USA.Suche in Google Scholar
[29] Lien EJ, Guo Z-R, Li R-L, et al. Use of dipole moment as a parameter in drug-receptor interaction and quantitative structure-activity relationship studies. J Pharm Sci. 1982;71:641–55.10.1002/jps.2600710611Suche in Google Scholar PubMed
[30] Shi F, Li Z, Kong L, et al. Synthesis and crystal structure of 6-fluoro-3-hydroxypyrazine-2-carboxamide. Drug Discov Ther. 2014;8:117–20.10.5582/ddt.2014.01028Suche in Google Scholar PubMed
[31] Joseph T, Varghese HT, Panicker CY, et al. Vibrational spectroscopic investigations and computational study of 5-tert-Butyl-N-(4-trifluoromethylphenyl) pyrazine-2-carboxamide. Spectrochim Acta A. 2013;113:203–14.10.1016/j.saa.2013.04.101Suche in Google Scholar
[32] Sakthivel S, Alagesan T, Al-Saadi AA, et al. Vibrational spectra of 3,5-diamino-6-chloro-N-(diaminomethylene) pyrazine-2-carboxamide: combined experimental and theoretical studies. Spectrochim Acta A. 2014;127:157–67.10.1016/j.saa.2014.02.066Suche in Google Scholar PubMed
[33] Lukose J, Panicker CY, Nayak PS, et al. Synthesis, structural and vibrational investigation on 2-phenyl-N-(pyrazin-2-yl)acetamide combining XRD diffraction, FT-IR and NMR spectroscopies with DFT calculations. Spectrochim Acta A. 2015;135:608–16.10.1016/j.saa.2014.07.004Suche in Google Scholar PubMed
[34] Runge E, Gross EKU. Density-functional theory for time-dependent systems. Phys Rev Lett. 1984;52:997–1000.10.1103/PhysRevLett.52.997Suche in Google Scholar
[35] Atkins PW, De Paula J. Atkins’ physical chemistry. Oxford: Oxford University Press; 2001.Suche in Google Scholar
[36] Hoffmann R, Schleyer P, Schaefer HF. Predicting molecules—more realism, please!. Angew Chem Int Ed. 2008;47:7164–7.10.1002/anie.200801206Suche in Google Scholar PubMed
[37] Smither SJ, Eastaugh LS, Steward JA, et al. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Res. 2014;104:153–5.10.1016/j.antiviral.2014.01.012Suche in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (DOI:https://doi.org/10.1515/psr-2017-0198).
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Artikel in diesem Heft
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