Computational Investigation of Withania somnifera Compounds Targeting S. pombe SMN YG-Dimer in Spinal Muscular Atrophy: Insights from Molecular Docking Analysis

Year : 2024 | Volume : 13 | Issue : 02 | Page : 39 52
    By

    Gayatri Tummalapenta,

  1. Student, Btech. Biotechnology, SRM University, KTR branch,, Tamil Nadu, India

Abstract

Objectives: The primary objective of this study is to determine the potential of phytochemical constituents of Withania somnifera in treating spinal muscular atrophy, an autosomal recessive genetic neurodegenerative disorder, through computational techniques. To investigate the binding affinity of phytocompound to the target protein S. pombe SMN YG-Dimer through molecular docking. Besides, evaluating the pharmacological attributes of phytochemical constituents to assess their ability as an ideal prospect for developing therapeutic medication. The target protein S. pombe SMN YG-Dimer of PDB ID: 4RG5 was extracted and downloaded from the Protein Data Bank (PDB) database. Later, the phytocompounds were extracted and downloaded from the IMPPAT database. The Swiss ADME webserver was used for evaluating the pharmacological properties and pharmacokinetics of phytocompounds. Finally, molecular docking was achieved by the PyRx webserver. Results: Molecular docking analysis revealed that withasomnine emerged as the most favorable phytocompound among other selected phytocompounds. Withasomnine demonstrated a significant binding affinity of -7.9 towards the target protein, indicating the need for further investigation. Moreover, withasomnine exhibited favorable pharmacological properties and pharmacokinetic profiles, positioning it as a promising candidate for drug development. Conclusion: The phytocompound withasomnine with the highest binding affinity to the target protein indicates a promising prospect for developing a therapeutic medication for treating spinal muscular atrophy

Keywords: Spinal muscular atrophy, S. pombe SMN YG-Dimer, Withania somnifera, phytocompound, molecular docking, ADMET analysis

[This article belongs to Research and Reviews : Journal of Computational Biology ]

How to cite this article:
Gayatri Tummalapenta. Computational Investigation of Withania somnifera Compounds Targeting S. pombe SMN YG-Dimer in Spinal Muscular Atrophy: Insights from Molecular Docking Analysis. Research and Reviews : Journal of Computational Biology. 2024; 13(02):39-52.
How to cite this URL:
Gayatri Tummalapenta. Computational Investigation of Withania somnifera Compounds Targeting S. pombe SMN YG-Dimer in Spinal Muscular Atrophy: Insights from Molecular Docking Analysis. Research and Reviews : Journal of Computational Biology. 2024; 13(02):39-52. Available from: https://journals.stmjournals.com/rrjocb/article=2024/view=180797


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References

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  27. Meng X-Y, Zhang H-X, Mezei M, Cui M. Molecular docking: A powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011;7(2):146–157. doi:2174/157340911795677602.
  1. Hahnen E, Schönling J, Rudnik-Schöneborn S, Zerres K, Wirth B. Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease. Am J Hum Genet. 1996;59(5):1057.
  2. National Institute of Neurological Disorders and Stroke. (2024). Spinal muscular atrophy [Online]. National Institute of Neurological Disorders and Stroke. Available from: https://www.ninds.
    gov/health-information/disorders/spinal-muscular-atrophy.
  3. Armengol VD, Darras BT, Abulaban AA, Alshehri A, Barisic N, Ben-Omran T, Bernert G, Castiglioni C, Chien YH, Farrar MA, Kandawasvika G. Life-saving treatments for spinal muscular atrophy: global access and availability. Neurol Clin Pract. 2024;14(1):e200224. doi:10.1212/CPJ.0000000000200224.
  4. Levchenko M, Gou Y, Graef F, Hamelers A, Huang Z, Ide-Smith M, Iyer A, Kilian O, Katuri J, Kim JH, Marinos N. Europe PMC in 2017. Nucleic Acids Res. 2018;46(D1):D1254–D2 doi:10.1093/nar/gkx1005.
  5. Rudnik-Schöneborn S, Zerres K. Spinal muscular atrophies. Inte Neurol Clin 2009;208–211.
  6. Hodgkinson VL, Oskoui M, Lounsberry J, M’Dahoma S, Butler E, Campbell C, MacKenzie A, McMillan HJ, Simard L, Vajsar J, Brais B. A national spinal muscular atrophy registry for real-world evidence. Can J Neurol Sci. 2020;47(6):810–81 doi:10.1017/cjn.2020.111.
  7. Park HB, Lee SM, Lee JS, Park MS, Park KI, Namgung R, Lee C. Survival analysis of spinal muscular atrophy type I. Korean J Pediatr. 2010;53(11):965. doi:3345/kjp.2010.53.11.965.
  8. Rubinstein WS, Maglott DR, Lee JM, Kattman BL, Malheiro AJ, Ovetsky M, Hem V, Gorelenkov V, Song G, Wallin C, Husain N. The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency. Nucleic Acids Res. 2012;41(D1):D925–D9 doi:10.1093/nar/gks1173.
  9. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis. 2011;6:71. doi:1186/1750-1172-6-7.
  10. Keinath MC, Prior DE, Prior TW. Spinal muscular atrophy: mutations, testing, and clinical r Appl Clin Genet. 2021;14:11–25. doi:10.2147/TACG.S239603.
  11. Ogbonmide T, Rathore R, Rangrej SB, Hutchinson S, Lewis M, Ojilere S, Carvalho V, Kelly I. Gene therapy for spinal muscular atrophy (SMA): A review of current challenges and safety considerations for onasemnogene abeparvovec (Zolgensma). Cureus. 2023;15(3):e36197. doi:7759/cureus.36197.
  12. Porensky PN, Burghes AHM. Antisense oligonucleotides for the treatment of spinal muscular atrophy. Hum Gene Ther 2013;24(5):489–4 doi:10.1089/hum.2012.225.
  13. Kakazu J, Walker NL, Babin KC, Trettin KA, Lee C, Sutker PB, et al. Risdiplam for the use of spinal muscular atrophy. Orthop Rev (Pavia) 2021;13(2). Availaborg/10.52965/001c.25579
  14. Saleem S, Muhammad G, Hussain MA, Altaf M, Bukhari SNA. Withania somnifera L.: Insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iran J Basic Med Sci 2020;23(12):1501–15 doi:10.22038/IJBMS.2020.44254.10378.
  15. Singh N, Bhalla M, De Jager P, Gilca M. An overview on ashwagandha: A rasayana (Rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5S):208. org/10.4314/ajtcam.v8i5s.9.
  16. Mikulska P, Malinowska M, Ignacyk M, Szustowski P, Nowak J, Pesta K, et al. Ashwagandha (Withania somnifera)—current research on the health-promoting activities: A narrative review. Pharmaceutics. 2023;15(4):1057. doi:3390/pharmaceutics15041057.
  17. Syed AA, Reza MI, Singh P, Thombre GK, Gayen JR. Withania somnifera in neurological disorders: ethnopharmacological evidence, mechanism of action and its progress in delivery s Curr Drug Metab. 2021;22(7):561–571.
  18. Singh M, Ramassamy C. In vitro screening of neuroprotective activity of Indian medicinal plant Withania somnifera. J Nutr Sci. 2017;6:e54. doi:10.1017/jns.2017.48.
  19. Shah Z, Raghavan A. Withania somnifera: a pre-clinical study on neuroregenerative therapy for stroke. Neural Regen Res. 2015;10(2):183. doi:4103/1673-5374.152362.
  20. Gupta M, Kaur G. Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation. BMC Complement Altern Med. 2019;19(1). doi:1186/s12906-019-2635-0.
  21. Laskowski RA, Jabłońska J, Pravda L, Vařeková RS, Thornton JM. PDBsum: Structural summaries of PDB entries. Protein Sci. 2018;27(1):129–1 doi:10.1002/pro.3289.
  22. Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, Chand RPB, Aparna SR, Mangalapandi P, et al. IMPPAT: A curated database of Indian medicinal plants, phytochemistry and t Sci Rep. 2018;8(1). doi:10.1038/s41598-018-22631-z.
  23. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1). doi:1038/srep42717.
  24. Benet LZ, Hosey CM, Ursu O, Oprea TI. BDDCS, the rule of 5 and drugability. Adv Drug Deliv Rev. 2016;101:89–98. doi:1016/j.addr.2016.05.007.
  25. Dayangaç-Erden D, Bora G, Ayhan P, Kocaefe Ç, Dalkara S, Yelekçi K, et al. Histone deacetylase inhibition activity and molecular docking of (E)‐resveratrol: Its therapeutic potential in spinal muscular atrophy. Chem Biol Drug Des. 2009;73(3):355–3
  26. Konar A, Gupta R, Shukla RK, Maloney B, Khanna VK, Wadhwa R, et al. M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration, and memory recovery by i-Extract from Withania somnifera. Sci 2019;9(1):1–15.
  27. Meng X-Y, Zhang H-X, Mezei M, Cui M. Molecular docking: A powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011;7(2):146–157. doi:2174/157340911795677602.
Regular Issue Subscription Original Research
Volume 13
Issue 02
Received 15/05/2024
Accepted 14/10/2024
Published 04/11/2024
Publication Time 173 Days
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