Can the Antivirals Remdesivir and Favipiravir Work Better Jointly?
                        In Silico Insights

Cemal Parlak; Özgür Alver; Cecil N.M. Ouma; Lydia Rhyman; Ponnadurai Ramasami

doi:10.1055/a-1585-1323

Drug Research, Inhaltsverzeichnis

Drug Res (Stuttg) 2022; 72(01): 34-40
DOI: 10.1055/a-1585-1323

Original Article

Can the Antivirals Remdesivir and Favipiravir Work Better Jointly? In Silico Insights

Cemal Parlak

¹Department of Physics, Science Faculty, Ege University, Izmir, Turkey

,

Özgür Alver

²Department of Physics, Science Faculty, Eskisehir Technical University, Eskisehir, Turkey

,

Cecil N.M. Ouma

³HySA-Infrastructure CoC, North-West University, Faculty of Engineering, Potchefstroom, South Africa

,

Lydia Rhyman

⁴Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, Mauritius

⁵Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, Doornfontein Campus, Johannesburg, South Africa

,

Ponnadurai Ramasami

⁴Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, Mauritius

⁵Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, Doornfontein Campus, Johannesburg, South Africa

› Institutsangaben

Abstract

The proverb “Old is gold” is applicable in drug discovery and the proverb “All that Glitters is not Gold” is also appropriate. In the COVID-19 era, there has been a race for drugs to be effective against SARS-CoV-2. There are reports about the uses of Remdesivir and Favipiravir as existing antivirals against virus but none have been conclusive so far. In the attempts for innovations, the combination of drugs is also under trials. Therefore, we used the density functional theory method and quantum theory of atoms in molecules to investigate drug-drug interactions involving Remdesivir and Favipiravir. The computed parameters were related to the antiviral actions of both drugs together. The results indicate enhanced antiviral activity and it will be worthy to consider additional investigations with the combination of these two drugs.

Graphical Abstract

Key words

Remdesivir - Favipiravir - Drug–drug interaction - DFT - QTAIM

Volltext

Referenzen

References
1 Kennedy DA, Read AF. Why does drug resistance readily evolve but vaccine resistance does not?. Proc. R. Soc. B 2017; 284: 20162562
2 Lu DY. Personalized Cancer Chemotherapy: An Effective Way of Enhancing Outcomes in Clinics. Woodhead Publishing; UK: Page 37 2015
3 Schmid A, Wolfensberger A, Nemeth J, Schreiber PW, Sax H, Kuster SP. Monotherapy versus combination therapy for multidrug-resistant Gram-negative infections: Systematic Review and Meta-Analysis. Scientific Reports 2019; 9: 15290
4 Kupferschmidt K, Cohen J. Race to find COVID-19 treatments accelerates. Science 2020; 367: 1412-1413
5 Elmezayen AD, Al-Obaidi A, Şahin AT, Yelekçi K. Drug repurposing for coronavirus (COVID-19): In silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes, J Biomol Struct Dyn 2020; DOI: 10.1080/07391102.2020.1758791
6 Vicidomini C, Roviello V, Roviello GN. Molecular Basis of the Therapeutical Potential of Clove (Syzygium aromaticum L.) and Clues to Its Anti-COVID-19 Utility. Molecules 2021; 26: 1880
7 Sheahan TP, Sims AC, Graham RL. et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017; 9: eaal3653
8 Lo MK, Jordan R, Arvey A. et al. GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci Rep 2017; 7: 43395
9 Grein J, Ohmagari N, Shin D. et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19, N Engl J Med 2020. DOI: 10.1056/NEJMoa2007016
10 Caoa YC, Denga QX, Daib SX. Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence, Travel Medicine and Infectious Disease 2020. DOI: 10.1016/j.tmaid.2020.101647
11 Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S, Hall MD. Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19. ACS Cent Sci. 2020
12 Ko WC, Rolain JM, Lee NY, Chen PL, Huang CT, Lee PI, Hsueh PR. Arguments in favour of remdesivir for treating SARS-CoV-2 infections, International Journal of Antimicrobial Agents 2020. DOI: 10.1016/j.ijantimicag.2020.105933
13 Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu Y, Li M, Li X, Zheng M, Chen L, Li H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharm Sin B 2020. DOI: 10.1016/j.apsb.2020.02.008
14 Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res 2013; 100: 446-454
15 Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, Nomura N, Egawa H, Minami S, Watanabe Y, Narita H, Shiraki K. In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother 2002; 46: 977-981
16 Furuta Y, Takahashi K, Kuno-Maekawa M, Sangawa H, Uehara S, Kozaki K, Nomura N, Egawa H, Shiraki K. Mechanism of action of T-705 against influenza virus. Antimicrob Agents Chemother 2005; 49: 981-986
17 Du YX, Chen XP. Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019-nCoV Infection, Clinical Pharmacology & Therapeutics 2020; DOI: 10.1002/cpt.1844
18 Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discoveries & Therapeutics 2020; 14: 58-60
19 Cai Q, Yang M, Liu D. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study, Engineering 2020; DOI: 10.1016/j.eng.2020.03.007
20 Flynn E. Drug-Drug Interactions. xPharm: The Comprehensive Pharmacology Reference. Editör: Enna, SJ Bylund, DB.. Boston: Elsevier; pages 1-3, 2007
21 Zhou X, Dai E, Song Q, Ma X, Meng Q, Jiang Y, Jiang W. In silico drug repositioning based on drug-miRNA associations. Briefings in Bioinformatics 2020; 21: 498-510
22 Mehdipour AR, Safarpour AM, Taghavi F, Jamali M. Density functional theory-based Quantitative Structure Activity Relationship (QSAR) study of alkanol and alkanthiol derivatives. QSAR Combi Sci 2009; 28: 568-575
23 Paulino M, Alvareda EM, Denis PA, Barreiro EJ, Sperandio da Silva GM, Dubin M, Gastellú C, Aguilera S, Tapia O. Studies of trypanocidal (inhibitory) power of naphthoquinones: Evaluation of quantum chemical molecular descriptors for structure-activity relationships. . Eur J Med Chem 2008; 43: 2238-2246
24 Behzadi H, Roonasi P, Taghipou KA, van der Spoel D, Manzetti S. Relationship between electronic properties and drug activity of seven quinoxaline compounds: A DFT study. J Mol Struct 2015; 1091: 196-202
25 Pinzi L, Rastelli G. Molecular Docking: Shifting Paradigms in Drug Discovery. Int J Mol Sci 2019; 20: 4331
26 Bader RFW. In Atoms in Molecules: A Quantum Theory. Oxford: Clarendon Press; 1990
27 Grabowski SJ. What Is the Covalency of Hydrogen Bonding?. Chem Rev 2011; 111: 2597-2625
28 Matta CF, Boyd RJ. The Quantum Theory of Atoms in Molecules, From Solid State to DNA and Drug Design. WILEY-VCH Verlag GmbH & Co. KGaA; Weinheim: 2007
29 Interaction of Vitamin B3 with Parent Uracil and Anticancer Uracils: A Detailed Computational Approach. Org Chem Res. 2020 6. 36-53
30 Matta CF, Arabi AA. Electron density descriptors as predictors in quantitative structure – activity / property relationships and drug design. Future Med Chem 2011; 3: 969-994
31 Khrenova MG, Krivitskayaac AV, Tsirelson VG. The QM/MM-QTAIM approach reveals the nature of the different reactivity of cephalosporins in the active site of L1 metallo-b-lactamase. New J Chem 2019; 43: 7329-7338
32 Parthasarthi R, Subramanian V, Sathyamurthy N. Hydrogen Bonding without Borders: An Atoms-in-Molecules Perspective. J Phys Chem A 2006; 110: 3349-3351
33 Rozas I, Alkorta I, Elguero J. Behavior of Ylides Containing N, O, and C Atoms as Hydrogen Bond Acceptors. J Am Chem Soc 2000; 122: 11154-11161
34 Borbone N, Piccialli G, Roviello GN, Oliviero G. Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses. Molecules 2021; 26: 986
35 Rhyman L, Tursun M, Abdallah HH, Choong YS, Parlak C, Kharkar P, Ramasami P. Theoretical investigation of the derivatives of favipiravir (T-705) as potential drugs for Ebola virus. Physical Sciences Reviews 2018; 3: 20170198
36 Alver Ö, Parlak C, Umar Y, Ramasami P. DFT/QTAIM analysis of favipiravir adsorption on pristine and silicon doped C20 fullerenes. Main Group Met Chem 2019; 42: 143-149
37 Parlak C, Alver Ö. A density functional theory investigation on amantadine drug interaction with pristine and B, Al, Si, Ga, Ge doped C60 fullerenes. Chem Phys Lett 2017; 678: 85-90
38 Parr RG, Yang W. Density-functional Theory of Atoms and Molecules. Oxford: Oxford Univ. Press; 1989
39 Becke AD. A new mixing of Hartree-Fock and local density-functional theories. J Chem Phys 1993; 98: 1372-1377
40 Tomasi J, Mennucci B, Cammi R. Quantum mechanical continuum solvation models. Chem Rev 2005; 105: 2999-3093
41 Padmanabhan J, Parthasarathi R, Subramanian V, Chattaraj PK. Electrophilicity-Based Charge Transfer Descriptor. J Phys Chem A 2007; 111: 1358-1361
42 Frisch MJ, Trucks GW, Schlegel HB. et al. Gaussian 09, Revision A.1, Gaussian Inc., Wallingford, CT, 2009
43 Dennington R, Keith T, Millam J. Gauss View, Version 5, Semichem Inc.. Shawnee Mission: KS; 2009
44 Lu T, Chen F. Multiwfn: A multifunctional wavefunction analyser. J Comput Chem 2012; 33: 580-592
45 Nagy Á, Parr RG. Local virial theorem in density-functional theory. Phys Rev A. 1990; 42: 201-203
46 Fukui K. Role of Frontier Orbitals in Chemical Reactions. Science 1982; 218: 747-754
47 Ayala PY, Scuseria GE. Linear scaling second-order Moller–Plesset theory in the atomic orbital basis for large molecular systems. J Chem Phys 1999; 110: 3660
48 Bhattacharjee AK, Skanchy DJ, Jennings B, Hudson TH, Brendle JJ, Werbovetz KA. Analysis of stereoelectronic properties, mechanism of action and pharmacophore of synthetic indolo[2,1-b]quinazoline-6,12-dione derivatives in relation to antileishmanial activity using quantum chemical, cyclic voltammetry and 3-D-QSAR CATALYST procedures. Bioorgan. Med Chem 2002; 10: 1979-1989
49 Kelleni MT. Tocilizumab, Remdesivir, Favipiravir, and Dexamethasone Repurposed for COVID-19: a Comprehensive Clinical and Pharmacovigilant Reassessment, SN Compr. Clin Med 2021; 3: 919-923
50 Marcolino VA, Pimentel TC, Barão CE. What to expect from different drugs used in the treatment of COVID-19: a study on applications and in vivo and in vitro results. Eur J Pharmacol 2020; 887: 173467
51 Carothers C, Birrer K, Vo M. Acetylcysteine for the treatment of suspected remdesivir-associated acute liver failure in COVID-19: a case series. Pharmacotherapy 2020; 40: 1166-1171
52 Suliman FO, Al-Nafai I, Al-Busafi SN. Synthesis, characterization and DFT calculation of 4-fluorophenyl substituted tris(8-hydroxyquinoline)aluminum(III) complexes, Spectrochim. Acta A 2014; 118: 66-72
53 Kawakami J, Kakinami H, Matsushima N, Nakane A, Kitahara H, Nagaki M, Ito S. Structure–activity Relationship Analysis for Antimicrobial Activities of Tryptanthrin Derivatives Using Quantum Chemical Calculations. J Comput Chem Jpn 2013; 12: 109-112

Zusatzmaterial

Supplementary Material