• ISSN 1674-8301
  • CN 32-1810/R
Volume 35 Issue 6
Nov.  2021
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Article Contents
Adittya Arefin, Tanzila Ismail Ema, Tamnia Islam, Md. Saddam Hossen, Tariqul Islam, Salauddin Al Azad, Md. Nasir Uddin Badal, Md. Aminul Islam, Partha Biswas, Nafee Ul Alam, Enayetul Islam, Maliha Anjum, Afsana Masud, Md. Shaikh Kamran, Ahsab Rahman, Parag Kumar Paul. Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection: an in silico approach[J]. The Journal of Biomedical Research, 2021, 35(6): 459-473. doi: 10.7555/JBR.35.20210111
Citation: Adittya Arefin, Tanzila Ismail Ema, Tamnia Islam, Md. Saddam Hossen, Tariqul Islam, Salauddin Al Azad, Md. Nasir Uddin Badal, Md. Aminul Islam, Partha Biswas, Nafee Ul Alam, Enayetul Islam, Maliha Anjum, Afsana Masud, Md. Shaikh Kamran, Ahsab Rahman, Parag Kumar Paul. Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection: an in silico approach[J]. The Journal of Biomedical Research, 2021, 35(6): 459-473. doi: 10.7555/JBR.35.20210111

Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection: an in silico approach

doi: 10.7555/JBR.35.20210111
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  • Corresponding author: Salauddin Al Azad, Fermentation Engineering Major, School of Biotechnology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China. Tel: +88-01943187581, E-mail: sci.01866952382@gmail.com
  • Received: 2021-07-02
  • Revised: 2021-09-10
  • Accepted: 2021-09-13
  • Published: 2021-11-06
  • Issue Date: 2021-11-28
  • Lassa hemorrhagic fever, caused by Lassa mammarenavirus (LASV) infection, accumulates up to 5000 deaths every year. Currently, there is no vaccine available to combat this disease. In this study, a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block the α-dystroglycan (α-DG) receptor and prevent LASV influx. Following rigorous absorption, distribution, metabolism, and excretion (ADME) and quantitative structure-activity relationship (QSAR) profiling, molecular docking was conducted with the top ligands against the α-DG receptor. The compounds chrysin, reticuline, and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding affinity. Post-docking analysis revealed that interactions with Arg76, Asn224, Ser259, and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of ligands. Molecular dynamics simulation was performed comprehensively to study the stability of the protein-ligand complexes. In-depth assessment of root-mean-square deviation (RMSD), root mean square fluctuation (RMSF), polar surface area (PSA), B-Factor, radius of gyration (Rg), solvent accessible surface area (SASA), and molecular surface area (MolSA) values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand complexes. To authenticate the potentialities of the ligands as target-specific drugs, an in vivo study is underway in real time as the continuation of the research.

     

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  • [1]
    Centers for Disease Control and Prevention. Lassa fever[EB/OL]. [2021-05-23]. https://www.cdc.gov/vhf/lassa/index.html.
    [2]
    Garry RF. 50 years of Lassa fever research[J]. Curr Top Microbiol Immunol, 2020. doi: 10.1007/82_2020_214. [Epub ahead of print
    [3]
    Brisse ME, Ly H. Hemorrhagic fever-causing arenaviruses: lethal pathogens and potent immune suppressors[J]. Front Immunol, 2019, 10: 372. doi: 10.3389/fimmu.2019.00372
    [4]
    Olayemi A, Cadar D, Magassouba N, et al. New hosts of the Lassa virus[J]. Sci Rep, 2016, 6: 25280. doi: 10.1038/srep25280
    [5]
    Bonwitt J, Sáez AM, Lamin J, et al. At home with Mastomys and Rattus: human-rodent interactions and potential for primary transmission of Lassa virus in domestic spaces[J]. Am J Trop Med Hyg, 2017, 96(4): 935–943. doi: 10.4269/ajtmh.16-0675
    [6]
    Andersen KG, Shapiro BJ, Matranga CB, et al. Clinical sequencing uncovers origins and evolution of Lassa virus[J]. Cell, 2015, 162(4): 738–750. doi: 10.1016/j.cell.2015.07.020
    [7]
    Torriani G, Galan-Navarro C, Kunz S. Lassa virus cell entry reveals new aspects of virus-host cell interaction[J]. J Virol, 2017, 91(4): e01902–16. doi: 10.1128/jvi.01902-16
    [8]
    Oppliger J, Torriani G, Herrador A, et al. Lassa virus cell entry via dystroglycan involves an unusual pathway of macropinocytosis[J]. J Virol, 2016, 90(14): 6412–6429. doi: 10.1128/jvi.00257-16
    [9]
    Fedeli C, Torriani G, Galan-Navarro C, et al. Axl can serve as entry factor for Lassa virus depending on the functional glycosylation of dystroglycan[J]. J Virol, 2017, 92(5): e01613–17. doi: 10.1128/jvi.01613-17
    [10]
    Moraz ML, Pythoud C, Turk R, et al. Cell entry of Lassa virus induces tyrosine phosphorylation of dystroglycan[J]. Cell Microbiol, 2013, 15(5): 689–700. doi: 10.1111/cmi.12078
    [11]
    Agnihothram SS, York J, Nunberg JH. Role of the stable signal peptide and cytoplasmic domain of G2 in regulating intracellular transport of the Junín virus envelope glycoprotein complex[J]. J Virol, 2006, 80(11): 5189–5198. doi: 10.1128/jvi.00208-06
    [12]
    Oscherwitz J. The promise and challenge of epitope-focused vaccines[J]. Hum Vaccin Immunother, 2016, 12(8): 2113–2116. doi: 10.1080/21645515.2016
    [13]
    Dey D, Paul PK, Azad SA, et al. Molecular optimization, docking, and dynamic simulation profiling of selective aromatic phytochemical ligands in blocking the SARS-CoV-2 S protein attachment to ACE2 receptor: an in silico approach of targeted drug designing[J]. J Adv Vet Anim Res, 2021, 8(1): 24–35. doi: 10.5455/javar.2021.h481
    [14]
    Tang K, He S, Zhang X, et al. Tangeretin, an extract from Citrus peels, blocks cellular entry of arenaviruses that cause viral hemorrhagic fever[J]. Antiviral Res, 2018, 160: 87–93. doi: 10.1016/j.antiviral.2018.10.011
    [15]
    Endo T. Dystroglycans[J]. Compr Glycosci, 2007, 3: 285–296. doi: 10.1016/b978-044451967-2/00052-0
    [16]
    Lv F, Li Z, Hu W, et al. Small molecules enhance functional O-mannosylation of alpha-dystroglycan[J]. Bioorg Med Chem, 2015, 23(24): 7661–7670. doi: 10.1016/j.bmc.2015.11.011
    [17]
    Tang K, Zhang X, Chen Q, et al. Effects and mechanism of 3, 5, 6, 7, 4'-pentamethoxyflavone for blocking arenavirus entry[J]. Acta Pharm Sin (in Chinese), 2019, 54(5): 838–845. doi: 10.16438/j.0513-4870.2018-1152
    [18]
    Durán-Iturbide NA, Díaz-Eufracio BI, Medina-Franco JL. In silico ADME/Tox profiling of natural products: a focus on BIOFACQUIM[J]. ACS Omega, 2020, 5(26): 16076–16084. doi: 10.1021/acsomega.0c01581
    [19]
    Brandt BW, Heringa J, Leunissen JAM. SEQATOMS: a web tool for identifying missing regions in PDB in sequence context[J]. Nucleic Acids Res, 2008, 36(S2): W255–W259. doi: 10.1093/nar/gkn237
    [20]
    Wu Q, Peng Z, Zhang Y, et al. COACH-D: improved protein-ligand binding sites prediction with refined ligand-binding poses through molecular docking[J]. Nucleic Acids Res, 2018, 46(W1): W438–W442. doi: 10.1093/nar/gky439
    [21]
    Waterhouse A, Bertoni M, Bienert S, et al. SWISS-MODEL: homology modelling of protein structures and complexes[J]. Nucleic Acids Res, 2018, 46(W1): W296–W303. doi: 10.1093/nar/gky427
    [22]
    Covaceuszach S, Bozzi M, Bigotti MG, et al. Structural flexibility of human α-dystroglycan[J]. FEBS Open Bio, 2017, 7(8): 1064–1077. doi: 10.1002/2211-5463.12259
    [23]
    McPherson A, Cudney B. Optimization of crystallization conditions for biological macromolecules[J]. Acta Crystallogr F Struct Biol Commun, 2017, 70(Pt 11): 1445–1467. doi: 10.1107/S2053230X14019670
    [24]
    Yang Z, Lasker K, Schneidman-Duhovny D, et al. UCSF Chimera, MODELLER, and IMP: an integrated modeling system[J]. J Struct Biol, 2012, 179(3): 269–278. doi: 10.1016/j.jsb.2011.09.006
    [25]
    Kim S, Chen J, Cheng T, et al. PubChem in 2021: new data content and improved web interfaces[J]. Nucleic Acids Res, 2021, 49(D1): D1388–D1395. doi: 10.1093/nar/gkaa971
    [26]
    Gasteiger J, Marsili M. A new model for calculating atomic charges in molecules[J]. Tetrahedron Lett, 1978, 19(34): 3181–3184. doi: 10.1016/s0040-4039(01)94977-9
    [27]
    Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx[J]. Methods Mol Biol, 2015, 1263: 243–250. doi: 10.1007/978-1-4939-2269-7_19
    [28]
    Sharif A, Hossen S, Shaikat MM, et al. Molecular optimization, docking and dynamic simulation study of selective natural aromatic components to block E2-CD81 complex formation in predating protease inhibitor resistant HCV influx[J]. Int J Pharm Res, 2021, 13(2): 3511–3525. doi: 10.31838/ijpr/2021.13.02.408
    [29]
    Mysinger MM, Carchia M, Irwin JJ, et al. Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking[J]. J Med Chem, 2012, 55(14): 6582–6594. doi: 10.1021/jm300687e
    [30]
    Kuriata A, Gierut AM, Oleniecki T, ei al. CABS-flex 2.0: a web server for fast simulations of flexibility of protein structures[J]. Nucleic Acids Res, 2018, 46(W1): W338–W343. doi: 10.1093/nar/gky356
    [31]
    Yang J, Wang F, Chen Y, et al. LARMD: integration of bioinformatic resources to profile ligand-driven protein dynamics with a case on the activation of estrogen receptor[J]. Brief Bioinform, 2020, 21(6): 2206–2218. doi: 10.1093/bib/bbz141
    [32]
    Akter KM, Tushi T, Mily SJ, et al. RT-PCR mediated identification of SARS-CoV-2 patients from particular regions of Bangladesh and the multi-factorial analysis considering their pre and post infection health conditions[J]. Biotechnol J Int, 2020, 24(6): 43–56. doi: 10.9734/bji/2020/v24i630121
    [33]
    Islam R, Akter KM, Rahman A, et al. The serological basis of the correlation between iron deficiency anemia and thyroid disorders in women: a community based study[J]. J Pharm Res Int, 2021, 30(19A): 69–81. doi: 10.9734/jpri/2021/v33i19A31330
    [34]
    Al Azad S, Hossain KM, Rahman SMM, et al. In ovo inoculation of duck embryos with different strains of Bacillus cereus to analyse their synergistic post-hatch anti-allergic potentialities[J]. Vet Med Sci, 2020, 6(4): 992–999. doi: 10.1002/vms3.279
    [35]
    Rashaduzzaman M, Kamrujjaman M, Islam MA, et al. An experimental analysis of different point specific musculoskeletal pain among selected adolescent-club cricketers in Dhaka city[J]. Eur J Clin Exp Med, 2019, 17(4): 308–314. http://yadda.icm.edu.pl/yadda/element/bwmeta1.element.mhp-c0740d1d-18aa-4913-951b-f134cdd3ad86
    [36]
    Krieger E, Vriend G. New ways to boost molecular dynamics simulations[J]. J Comput Chem, 2015, 36(13): 996–1007. doi: 10.1002/jcc.23899
    [37]
    Alli A, Ortiz JF, Fabara SP, et al. Management of Lassa fever: a current update[J]. Cureus, 2021, 13(5): e14797. doi: 10.7759/cureus.14797
    [38]
    Cameron CE, Castro C. The mechanism of action of ribavirin: lethal mutagenesis of RNA virus genomes mediated by the viral RNA-dependent RNA polymerase[J]. Curr Opin Infect Dis, 2001, 14(6): 757–764. doi: 10.1097/00001432-200112000-00015
    [39]
    Braun-Sand SB, Peetz M. Inosine monophosphate dehydrogenase as a target for antiviral, anticancer, antimicrobial and immunosuppressive therapeutics[J]. Future Med Chem, 2010, 2(1): 81–92. doi: 10.4155/fmc.09.147
    [40]
    Jain J, Almquist SJ, Ford PJ, et al. Regulation of inosine monophosphate dehydrogenase type I and type II isoforms in human lymphocytes[J]. Biochem Pharmacol, 2004, 67(4): 767–776. doi: 10.1016/j.bcp.2003.09.043
    [41]
    Moreno H, Gallego I, Sevilla N, et al. Ribavirin can Be mutagenic for arenaviruses[J]. J Virol, 2011, 85(14): 7246–7255. doi: 10.1128/jvi.00614-11
    [42]
    Hansen F, Jarvis MA, Feldmann H, et al. Lassa virus treatment options[J]. Microorganisms, 2021, 9(4): 772. doi: 10.3390/microorganisms9040772
    [43]
    Liu Y, Guo J, Cao J, et al. Screening of botanical drugs against Lassa virus entry[J]. J Virol, 2021, 95(8): e02429–20. doi: 10.1128/jvi.02429-20
    [44]
    Wang P, Liu Y, Zhang G, et al. Screening and identification of Lassa virus entry inhibitors from an FDA-approved drug library[J]. J Virol, 2018, 92(16): e00954–18. doi: 10.1128/jvi.00954-18
    [45]
    Zhang X, Tang K, Guo Y. The antifungal isavuconazole inhibits the entry of Lassa virus by targeting the stable signal peptide-GP2 subunit interface of Lassa virus glycoprotein[J]. Antiviral Res, 2020, 174: 104701. doi: 10.1016/j.antiviral.2019.104701
    [46]
    Kineta Inc. LHF-535 information[EB/OL]. [2021-03-25]. http://kinetabio.com/biodefense/lhf-535.
    [47]
    Madu IG, Files M, Gharaibeh DN, et al. A potent Lassa virus antiviral targets an arenavirus virulence determinant[J]. PLoS Pathog, 2018, 14(12): e1007439. doi: 10.1371/journal.ppat.1007439
    [48]
    De Vivo M, Masetti M, Bottegoni G, et al. Role of molecular dynamics and related methods in drug discovery[J]. J Med Chem, 2016, 59(9): 4035–4061. doi: 10.1021/acs.jmedchem.5b01684
    [49]
    Páll S, Zhmurov A, Bauer P, et al. Heterogeneous parallelization and acceleration of molecular dynamics simulations in GROMACS[J]. J Chem Phys, 2020, 153(13): 134110. doi: 10.1063/5.0018516
    [50]
    Fan H, Schneidman-Duhovny D, Irwin JJ, et al. Statistical potential for modeling and ranking of protein–ligand interactions[J]. J Chem Inf Model, 2011, 51(12): 3078–3092. doi: 10.1021/ci200377u
    [51]
    Zhao Y, Zeng C, Massiah MA. Molecular dynamics simulation reveals insights into the mechanism of unfolding by the A130T/V mutations within the MID1 zinc-binding bbox1 domain[J]. PLoS One, 2015, 10(4): e0124377. doi: 10.1371/journal.pone.0124377
    [52]
    Marsh JA, Teichmann SA. Relative solvent accessible surface area predicts protein conformational changes upon binding[J]. Structure, 2011, 19(6): 859–867. doi: 10.1016/j.str.2011.03.010
    [53]
    Geierhaas CD, Nickson AA, Lindorff-Larsen K, et al. BPPred: a Web-based computational tool for predicting biophysical parameters of proteins[J]. Protein Sci, 2007, 16(1): 125–134. doi: 10.1110/ps.062383807
    [54]
    Hitchcock SA, Pennington LD. Structure−brain exposure relationships[J]. J Med Chem, 2006, 49(26): 7559–7583. doi: 10.1021/jm060642i
    [55]
    Wager TT, Hou X, Verhoest PR, et al. Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties[J]. ACS Chem Neurosci, 2010, 1(6): 435–449. doi: 10.1021/cn100008c
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