Virtual screening for potential inhibitors of Lassa fever nucleoprotein

Main Article Content

Amaku James Friday
Kalu Kalu Igwe
Buhari Magaji

Abstract

Communication in Physical Sciences 2020, 5(3): 391-402


Authors: Amaku James Friday, Kalu Kalu Igwe and Buhari Magaji


Received 15 May 2020/Accepted 04 July 2020


The devastating impact of viral haemorrhagic fevers has deeply been felt in South America and Africa. This fever is caused by the
arenaviruses Lassa and has posed a matchless fight. Meanwhile, no effective drug or vaccine has been reported. Here we used virtual screening and molecular docking approach to identify a series of novel inhibitors (ZINC64450313 (-10.7 kcal/mol), ZINC00658482 (-10.5 kcal/mol), ZINC40789449 (-10.5 kcal/mol), ZINC14551223 (10.0 kcal/mol) and ZINC73892903 (10.0
kcal/mol)) that can exhibit significant binding affinity to Lassa fever nucleoprotein (PDB ID: 3mx5) than ribavirin (-6.7 kcal/mol). Swiss ADME web tools were used to assess the pharmacokinetics and drug-likeness characteristics of the lead molecule
(ZINC64450313). This assay showed that ZINC64450313 obeyed Lipinski, Egan, Verber and Muegge rules. However, pharmacokinetics predictions indicated that CYP1A2, CYP2C9, CYP2D6 and CYP2C19 isoenzyme were not inhibited by ZINC64450313. Toxicity assay of ZINC64450313 was acquired with an average similarity index of 33.25% and prediction
accuracy of 23% on the ProTox-II webserver. The lead molecule has an LD50 value of 10 mg/kg and belongs to toxicity class 2. The frontier molecular orbital’s analysis revealed that ZINC64450313 is more reactive than ribavirin due to the possesion
of better quantum chemical indices such as its the global hardness. Hence, an in vitro and in vivo assay of these molecules may proffer a pathway to finding effective inhibitors with the potential to truncate functional proteins responsible for the viral life cycle of arenaviruses Lassa. 

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Author Biographies

Amaku James Friday, Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria

Department of Chemistry,

Kalu Kalu Igwe , Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria

Departmemt of Veterinary Physiology,

Buhari Magaji , Gombe State University, Gombe State

Faculty of Science,

References

Abdullahi, M., Olotu, F. A., & Soliman, M. E. (2018). Allosteric inhibition abrogates dysregulated LFA-1 activation: Structural

insight into mechanisms of diminished immunologic disease. Computational biology and chemistry, 73, pp.49-56.

Ashburn, T. T., & Thor, K. B. (2004). Drug repositioning: identifying and developing new uses for existing drugs. Nature reviews Drug

discovery, 3, 8, pp.673-683.

Ayers, P. W., & Levy, M. (2000). Perspective on “Density functional approach to the frontierelectron theory of chemical reactivity”.

Theoretical Chemistry Accounts, 103, 3-4, pp.353-360.

Baize, S., Kaplon, J., Faure, C., Pannetier, D., Georges-Courbot, M.-C., & Deubel, V. (2004). Lassa virus infection of human

dendritic cells and macrophages is productive but fails to activate cells. The Journal of Immunology, 172, 5, pp. 2861-2869.

Becke, A. D. (2005). Real-space post-Hartree– Fock correlation models. The Journal of Chemical Physics, 122, 1-6, pp. 064101.

Bederka, L. H., Bonhomme, C. J., Ling, E. L., & Buchmeier, M. J. (2014). Arenavirus stable signal peptide is the keystone subunit for glycoprotein complex organization. MBio, 5, 6, pp. e02063-02014.

Carrillo-Bustamante, P., Nguyen, T. H. T., Oestereich, L., Günther, S., Guedj, J., & Graw, F. (2017). Determining Ribavirin’s mechanism of action against Lassa virus infection. Scientific reports, 7, 1, pp. 1-12.

Chattaraj, P. K., Chakraborty, A., & Giri, S. (2009). Net electrophilicity. The Journal of Physical Chemistry A, 113, 37, pp. 10068- 10074.

Cheng, F., Murray, J. L., & Rubin, D. H. (2016). Drug repurposing: new treatments for zika virus infection? Trends in molecular medicine, 22, 11, pp. 919-921.

Chermette, H. (1999). Chemical reactivity indexes in density functional theory. Journal of computational chemistry, 20, 1, pp. 129-154.

Dyall, J., Coleman, C. M., Hart, B. J., Venkataraman, T., Holbrook, M. R., Kindrachuk, J., Laidlaw, M. (2014). Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrobial agents and chemotherapy, 58, 8, pp. 4885-4893.

Gaussian09, R. A. (2009). M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Gonzalez, J.A. Pople, Gaussian 09, Revision E.01, Gaussian, Inc, Wallingford, CT, 2004. Inc., Wallingford CT, 121, pp. 150-166.

Gazquez, J. L., Cedillo, A., & Vela, A. (2007). Electrodonating and electroaccepting powers. The Journal of Physical Chemistry A, 111, 10, pp. 1966-1970.

Geerlings, P., De Proft, F., & Langenaeker, W. (2003). Conceptual density functional theory. Chemical Reviews, 103, 5, pp. 1793-1874.

Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeersch, T., Zurek, E., & Hutchison, G. R. (2012). Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. Journal of cheminformatics, 4, 1, pp.1-17.

Hastie, K. M., Zandonatti, M. A., Kleinfelter, L. M., Heinrich, M. L., Rowland, M. M., Chandran, K., Saphire, E. O. (2017). Structural basis for antibody-mediated neutralization of Lassa virus. Science, 356, 6341, pp. 923-928.

Houlihan, C., & Behrens, R. (2017). Lassa fever. Bmj, 358, 1-6, pp. j2986.

Johansen, L. M., DeWald, L. E., Shoemaker, C. J., Hoffstrom, B. G., Lear-Rooney, C. M., Stossel, A., Grenier, J. M. (2015). A screen of approved drugs and molecular probes identifies therapeutics with anti–Ebola virus activity. Science translational medicine, 7, 290, pp. 290ra289-290ra289.

Keenlyside, R. A., McCormick, J. B., Webb, P. A., Smith, E., Elliott, L., & Johnson, K. M. (1983). Case-control study of Mastomys natalensis and humans in Lassa virus-infected households in Sierra Leone. The American Journal of Tropical Medicine and Hygiene, 32, 4, 829-837.

Koes, D. R., & Camacho, C. J. (2012). ZINCPharmer: pharmacophore search of the ZINC database. Nucleic acids research,40(W1), W409-W414. Koopmans, T. (1934). Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den einzelnen Elektronen eines Atoms. Physica, 1, 1-6, pp. 104-113.

Kouznetsova, J., Sun, W., Martínez-Romero, C., Tawa, G., Shinn, P., Chen, C. Z., Zheng, W. (2014). Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs. Emerging microbes & infections, 3, 1, pp. 1-7.

Lukashevich, I. S., Maryankova, R., Vladyko, A.S., Nashkevich, N., Koleda, S., Djavani, M.,. Salvato, M. S. (1999). Lassa and mopeia virus replication in human monocytes/macrophages and in endothelial cells: Different effects on IL‐8 and TNF‐α gene expression. Journal of mMedical Virology, 59, 4, pp. 552-560.

Madrid, P. B., Chopra, S., Manger, I. D., Gilfillan, L., Keepers, T. R., Shurtleff, A. C., Davey, R. A. (2013). A systematic screen of FDAapproved drugs for inhibitors of biological threat agents. PLoS ONE, 8, 4, pp.1-9 . Mahanty, S., Hutchinson, K., Agarwal, S., Mcrae, M., Rollin, P. E., & Pulendran, B. (2003). Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. The Journal of Immunology, 170, 6,pp. 2797-2801.

McCormick, J., King, I., Webb, P., Scribner, C., Craven, R., Johnson, K., Belmont-Williams, R. (1986). Effective therapy with ribavirin.

New England Journal of Medicine, 314, pp.20-26.

McCormick, J. B., Walker, D. H., King, I. J., Webb, P. A., Elliott, L. H., Whitfield, S. G., & Johnson, K. M. (1986). Lassa virus hepatitis: a study of fatal Lassa fever in humans. The American journal of tropical medicine and hygiene, 35, 2, pp. 401-407.

Monath, T. P., Newhouse, V. F., Kemp, G. E., Setzer, H. W., & Cacciapuoti, A. (1974). Lassa virus isolation from Mastomys natalensis rodents during an epidemic in Sierra Leone. Science, 185, 4147, pp. 263-265.

Monteiro, A., Scotti, M., & Scotti, L. (2019). Molecular docking of fructose-derived nucleoside analogs against reverse transcriptase of HIV-1. Paper presented at the Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition.

Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., & Olson, A. J. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of computational chemistry, 19, 14,pp. 1639-1662.

Pandey, M., Muthu, S., & Gowda, N. N. (2017). Quantum mechanical and spectroscopic (FTIR, FT-Raman, 1H, 13C NMR, UV-Vis) studies, NBO, NLO, HOMO, LUMO and Fukui function analysis of 5-Methoxy-1Hbenzo [d] imidazole-2 (3H)-thione by DFT studies. Journal of Molecular Structure, 1130, pp. 511-521.

Patil, R., Das, S., Stanley, A., Yadav, L., Sudhakar, A., & Varma, A. K. (2010). Optimized hydrophobic interactions and hydrogen bonding at the target-ligand interface leads the pathways of drug-designing. PLoS ONE, 5, 8, pp. 1-8

Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera—a visualization system for exploratory research and analysis. Journal of computational chemistry, 25(13), 1605-1612.

Sahoo, M., Lingaraja Jena, S. D., & Kumar, S. (2016). Virtual screening for potential inhibitors of NS3 protein of Zika virus. Genomics & informatics, 14(3), 104.

Sbrana, E., Mateo, R. I., Xiao, S.-Y., Popov, V. L., Newman, P. C., & Tesh, R. B. (2006). Clinical laboratory, virologic, and pathologic changes in hamsters experimentally infected with Pirital virus (Arenaviridae): a rodent model of Lassa fever. The American journal of tropical medicine and hygiene, 74, 6, pp. 1096-1102.

Shimojima, M., Ströher, U., Ebihara, H., Feldmann, H., & Kawaoka, Y. (2012). Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry. Journal of virology, 86, 4, pp. 2067-2078.

Srivastava, K., Shimpi, M. R., Srivastava, A., Tandon, P., Sinha, K., & Velaga, S. P. (2016). Vibrational analysis and chemical activity of paracetamol–oxalic acid cocrystal based on monomer and dimer calculations: DFT and AIM approach. RSC Advances, 6, 12, pp. 10024-10037.

Walker, D., McCormick, J., Johnson, K., Webb, P., Komba-Kono, G., Elliott, L., & Gardner, J. (1982). Pathologic and virologic study of fatal Lassa fever in man. The American journal of pathology, 107,3, pp.349.

Yang, W., & Parr, R. G. (1985). Hardness, softness, and the fukui function in the electronic theory of metals and catalysis. Proceedings of the National Academy of Sciences, 82, 20, pp. 6723-6726.

Zhang, X., Yan, F., Tang, K., Chen, Q., Guo, J., Zhu, W., Guo, Y. (2019). Identification of a clinical compound losmapimod that blocks Lassa virus entry. Antiviral research, 167, pp.

-77.