Analysis of Ivermectin as Potential Inhibitor of SARS-CoV-2 Using Resonant Recognition Model

Author(s): Irena Cosic, Drasko Cosic, Ivan Loncarevic

With worldwide spread of COVID-19 disease caused by SARS-CoV-2 virus, everyone is trying to find effective cure. One of the quickest approaches is to test existing already approved and safe drugs for possibility of their activity against SARS-CoV-2 virus. One of such possible drugs is ivermectin, which is FDA approved broad spectrum anti parasitic agent. Recently it has been shown that ivermectin has broad range of in vitro antiviral activities and it has been shown that ivermectin is an inhibitor of SARS-CoV-2. We have previously used our recently developed extended Resonant Recognition Model (RRM) for small molecules and we have proposed hat drugs like hydroxychloroquine, chloroquine and remdesivir can interfere with SARS-CoV-2 viral infection. Here, we have used an extended RRM model for small molecules to analyze the possibility for ivermectin, an already FDA-approved drug, to interfere with SARS-CoV-2 viral activity, which could lead to an effective cure.

Drug Design, Small Molecules, Resonant Energy, Bioelectromagnetism, Resonant Recognition Model, SARS-Cov-2, COVID-19, Ivermectin

1. Cosic I, Cosic D, Loncarevic I: New Concept of Small Molecules Interaction with Proteins – An Application to Potential COVID-19 Drugs, International Journal of Sciences, 2020, 9(9), 16-25, doi: 10.18483/ijSci.2390.
2. Gonzales Canga A, Sahagun Prieto AM, Diez Liebana MJ, Fernandez Martinez N, Sierra Vega M, Garcia Vieitez JJ: The Pharmacokinetics and Interactions of Ivermectin in Humans – A Mini-Review. AAPS J, 2008; 10(1), 42-46.
3. Gotz V, Magar L, Dornfeld D, Giese S, Pohlmann A, Hoper D, Kong BW, Jans DA, Beer M, Haller O, Schwemmle M: Influenza A Viruses Escape from MxA Restriction at the Expense of Efficient Nuclear vRNNP Import. Scientific Reports, 2016; 6, 23138.
4. Lundberg L, Pinkham C, Baer A, Amaya M, Narayanan A, Wagstaff KM, Jans DA, Kehn-Hall K: Nuclear Import and Export Inhibitors Alter Capsid Protein Distribution in Mammalian Cells and Reduce Venezuelan Equine Encephalitis Virus Replication. Antiviral Research, 2013; 100(3), 662-672, doi: 10.1016/j.antiviral.2013.10.004.
5. Tay MYF, Fraser JE, Chan WKK, Moreland NJ, Rathore AP, Wang C, Vasudevan SG, Jans DA: Nuclear Localization of Dengue Virus (DENV) 1-4 Non-structural Protein 5, Protection Against All 4 DENV Serotypes by the Inhibitor Ivermectin. Antiviral Research, 2013; 301-306, doi: 10.1016/j.antiviral.2013.06.002.
6. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA: Ivermectin is a Specific Inhibitor of Importin α/β-mediated Nuclear Import Able to Inhibit Replication of HIV-1 and Dengue Virus. Biochemical Journal, 2012; 443(3), 851-856.
7. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM: The FDA-approved Drug Ivermectin Inhibits the Replication of SARS-CoV-2 in vitro. Antiviral Research, 2020; 178, 104787, doi: 10.1016/j.aniviral.2020.104787.
8. Cosic I: Macromolecular Bioactivity: Is it Resonant Interaction between Macromolecules? -Theory and Applications. IEEE Trans on Biomedical Engineering, 1994; 41, 1101-1114.
9. Cosic I: The Resonant Recognition Model of Macromolecular Bioactivity: Theory and Applications. Basel: Birkhauser Verlag, 1997.
10. Cosic I: Resonant Recognition Model of Protein-Protein and Protein-DNA Recognition, in Bioinstrumentation and Biosensors. Marcel Dekker Inc New York, 1990; 475-510.
11. Cosic I, Paspaliaris V, Cosic D: Biophysical Insights into Cystic Fibrosis Based on Electromagnetic Resonances in CFTR Proteins, International Journal of Sciences, 2019; 8(9), 1-8, doi: 10.18483/ijSci.2148.
12. Cosic I, Lazar K, Cosic D: Cellular Ageing - Telomere, Telomerase and Progerin analysed using Resonant Recognation Model. MD-Medical Data, 2014; 6(3), 205-209.
13. Cosic I, Cosic D, Lazar K: Analysis of Tumor Necrosis Factor Function Using the Resonant Recognition Model. Cell Biochemistry and Biophysics, 2015; doi: 10.1007/s12013-015-0716-3.
14. Cosic I, Paspaliaris V, Cosic D: Analysis of Protein-Receptor on an Example of Leptin-Leptin Receptor Interaction Using the Resonant Recognition Model. Appl. Sci., 2019; 9, 5169, doi: 10.3390/app9235169.
15. Cosic I, Cosic D, Loncarevic I: RRM Prediction of Erythrocyte Band3 Protein as Alternative Receptor for SARS-CoV-2. MDPI Appl. Sci., 2020; 10, 4053, doi: 10.3390/app10114053.
16. Cosic I, Lazar K, Cosic D: Prediction of Tubulin Resonant Frequencies Using the Resonant Recognition Model (RRM). IEEE Trans. on NanoBioscience, 2015; 12, 491-496; doi: 10.1109/TNB.2014.2365851.
17. Cosic I, Cosic D, Lazar K: Is It Possible to Predict Electromagnetic Resonances in Proteins, DNA and RNA? Nonlinear Biomedical Physics, 2015; 3, doi: 10.1140/s40366-015-0020-6.
18. Cosic I, Cosic D: The Treatment of Crigler-Najjar Syndrome by Blue Light as Explained by Resonant Recognition Model. EPJ Nonlinear Biomedical Physics, 2016; 4(9), doi: 10.1140/epjnbp/s40366-016-0036-6.
19. Cosic I, Cosic D, Lazar K: Environmental Light and Its Relationship with Electromagnetic Resonances of Biomolecular Interactions, as Predicted by the Resonant Recognition Model. International Journal of Environmental Research and Public Health, 2016; 13(7), 647, doi: 10.3390/ijeprh13070647.
20. Cosic I, Paspaliaris V, Cosic D: Explanation of Osteoblastic Differentiation of Stem Cells by Photo Biomodulation Using the Resonant Recognition Model. Appl. Sci., 2019; 9, 1979, doi: 10.3390/app9101979.
21. Vojisavljevic V, Pirogova E, Cosic I: The Effect of Electromagnetic Radiation (550nm-850nm) on I-Lactate Dehydrogenase Kinetics. Internat J Radiat Biol, 2007; 83, 221-230.
22. Dotta BT, Murugan NJ, Karbowski LM, Lafrenie RM, Persinger MA: Shifting Wavelength of Ultraweak Photon Emissions from Dying Melanoma Cells: Their Chemical Enhancement and Blocking Are Predicted by Cosic’s Theory of Resonant Recognition Model for Macromolecules. Naturwissenschaften, 2014; 101(2), doi: 10.1007/s00114-013-1133-3.
23. Murugan NJ, Karbowski LM, Persinger MA: Cosic’s Resonance Recognition Model for Protein Sequences and Photon Emission Differentiates Lethal and Non-Lethal Ebola Strains: Implications for Treatment. Open Journal of Biophysics, 2014; 5, 35.
24. Karbowski LM, Murugan NJ, Persinger MA: Novel Cosic Resonance (Standing Wave) Solutions for Components of the JAK-STAT Cellular Signalling Pathway: A Convergence of Spectral Density Profiles. FEBS Open Bio, 2015; 5, 245-250.
25. Veljkovic V, Slavic I: General Model od Pseudopotentials. Physical Review Letters, 1972; 29, 105-108.
26. Veljkovic V: A Theoretical Approach to Preselection of Cancerogens and Chemical Carcinogenesis. Gordon & Breach New York, 1980.
27. Veljkovic V: The Dependence of the Fermi Energy on the Atomic Number, Physics Letters, 1973; 45A(1), 41-42.
28. Mohsin ASM, Salim MB: Probing the Intracellular Refractive Index and Molecular Interaction of Gold Nanoparticles in HeLa Cells Using Single Particle Spectroscopy. International Journal of Nanomedicine, 2018; 13, 6019-6028, doi: 10.2147/IJN.S175523.
29. Li F: Receptor Recognition and Cross-species Infections of SARS Coronavirus. Antiviral Research, 2013; 100(1), 246–54, doi: 10.1016/j.antiviral.2013.08.014.
30. Krsmanovic V, Biquard JM, Sikorska-Walker M, Cosic I, Desgranges C, Trabaud MA, Whitfield JF, Durkin JP, Achour A, Hearn MT: Investigation Into the Cross-reactivity of Rabbit Antibodies Raised against Nonhomologous Pairs of Synthetic Peptides Derived from HIV-1 gp120 proteins. J.Peptide Res, 1998; 52(5), 410-412.
31. Hearn MTW, Biquard JM, Cosic I, Krsmanovic V: Peptides Immunologically related to proteins expressed by a viral agent, having a sequence of amino acids ordered by means of protein informational method. US Patent 6, 294, 174, 2001.
32. Achour A, Biquard JM, Krsmanovic V, M’Bika JP, Ficheux D, Sikorska M, Cozzone AJ: Induction of Human Immunodeficiency Virus (HIV-1) Envelope Specific Cell-Mediated Immunity by a Non-Homologus Synthetic Peptide. PLoS ONE, 2007; 11, 1-12, doi: 10.1371/journal.pone.0001214.