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Activity profiling of natural and synthetic SARS-Cov-2 inhibitors using molecular docking analysis

  • Emmanuel C. Ohaekenyem EMAIL logo , Chukwuebuka T. Onyema und Sunday E. Atawodi
Veröffentlicht/Copyright: 23. April 2024
Pure and Applied Chemistry
Aus der Zeitschrift Pure and Applied Chemistry Band 96 Heft 6

Abstract

COVID-19, the global pandemic caused by SARS-Corona virus 2 (SARS-CoV-2), recently ravaged the World with various efforts charged towards finding therapeutic drug targets for this novel virus. The identification of COVID-19 main protease (Mpro) opened the possibility of testing new families of inhibitors as potential anti-coronaviral drugs. Protein-drug interaction is of pivotal importance to understanding the structural features essential for any ligand affinity. This study evaluated the efficacy of an isolated bioactive plant compound and synthetic tetraazamacrocycles against COVID-19 Mpro by molecular docking. Molecular docking investigations were performed using PyRx, Auto Dock vina and Discovery Studio (DS) to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro (PDB ID: 6LU7: Resolution 2.16 Å) was docked with 1 flavonoid and 3 tetraaza-macrocyclic compounds comparatively with known anti-viral drugs (Remdesivir (REMD) and Nelfinavir (NELF)) and hydroxychloroquine (HCQ). Docking studies showed H-TEAD, 5 interacting with 5 residues having the highest binding affinity of −9.4 kcal/mol, followed by TEAD with 5 residue interactions and a binding affinity value of −9.4 kcal/mol, HA-TEAD, 7 has 5 interactions with a binding affinity of −9.3 kcal/mol, and Siam1 has 6 interactions with a binding energy of −7.8 kcal/mol. All the docked potential drugs have binding energies higher than the reference drugs HCQ, 1 and REMD, 2 connoting greater activity except NELF, 3 whose value is only lower than the 3 macrocycles (HA-TEAD, 7 and H-TEAD, 5 and TEA1, 6). They are bound through hydrogen bonds, arene-anion and arene-cation interactions. The trend of binding affinity show H-TEAD (−9.4 kcal/mol) = TEAD1 (−9.4 kcal/mol) > HA-TEAD (−9.3 kcal/mol) > NELF (−8.7 kcal/mol) > Siamone (−8.8 kcal/mol) > HCQ (−7.2 kcal/mol) > REMD (−6.2 kcal/mol) while the number of interactions shows REMD > HA-TEAD = HCQ > Siamone > NELF > H-TEAD > TEAD1. This study, hence, validates the activity of HCQ against COVID-19 and provides a foundation for advanced experimental research, to evaluate the real pharmaceutical potentials of these compounds, towards finding a cure for COVID-19 and other related diseases.

Keywords: 8th Annual Symposium ACS Nigeria Chapter; ADMET; IUPAC African Early Career Chemists Workshop; COVID-19; flavonoid; hydroxychloroquine; macrocycles; nelfinavir; remdesivir; SARS-CoV-2
Corresponding author: Emmanuel C. Ohaekenyem, Department of Pure and Industrial Chemistry, Faculty of Physical Sciences, Nnamdi Azikiwe University, Awka, Nigeria, Phone: +2347064421816, e-mail:
Article note: A collection of invited papers based on presentations at the African Early Career Chemists Workshop and 8th ACS Nigerian Chapter Symposium.

Acknowledgment

The authors acknowledge the assistance of Dr. Fortunatus Ezebuo throughout the research.

References

[1] J. Otrompke. Pharm. J. 293, 7833 (2014), https://doi.org/10.1211/PJ.2014.20066890.Suche in Google Scholar

[2] World Health Organization. SARS (Severe Acute Respiratory Syndrome) (2004), https://www.who.int/ith/diseases/sars/en/ (accessed Apr 16, 2020).Suche in Google Scholar

[3] J. Peiris, S. Lai, L. Poon, Y. Guan, L. Yam, W. Lim, K. Yuen. Lancet 9366(361), 1319 (2003), https://doi.org/10.1016/s0140-6736(03)13077-2.Suche in Google Scholar PubMed PubMed Central

[4] P. JSM, W. Lai, P. LLM, G. Yakan, Y. LYC, W. Lim. Tepecik Dergisi 1(13), 55 (2003), https://doi.org/10.5222/terh.2003.26734.Suche in Google Scholar

[5] World Health Organization. MERS Monthly Summary (2019), https://www.who.int/emergencies/mers-cov/en/ (accessed Apr 16, 2020).Suche in Google Scholar

[6] Centers for Disease Control and Prevention. SARS Basics Fact Sheet (2017), https://www.cdc.gov/sars/about/fs-sars.html (accessed Apr 16, 2020).Suche in Google Scholar

[7] L. L. Ren, Y. M. Wang, Z. Q. Wu, Z. C. Xiang, L. Guo, T. Xu, J. W. Wang. Chin. Med. J. 133, 1015 (2020), https://doi.org/10.1097/CM9.0000000000000722.Suche in Google Scholar PubMed PubMed Central

[8] C. Huang, Y. Wang, X. Li, L. Ren, J. Zhao, Y. Hu. Lancet 395(10223), 497 (2020), https://doi.org/10.1016/s0140-6736(20)30183-5.Suche in Google Scholar

[9] W. Wang, J. Tang, F. Wei. J. Med. Virol. 92(4), 441 (2020), https://doi.org/10.1002/jmv.25689.Suche in Google Scholar PubMed PubMed Central

[10] W. G. Carlos, C. S. Dela Cruz, B. Cao, S. Pasnick, S. Jamil. Am. J. Respir. Crit. Care Med. 201(4), 7 (2020), https://doi.org/10.1164/rccm.2014P7.Suche in Google Scholar PubMed

[11] C. I. Paules, H. D. Marston, A. S. Fauci. JAMA 323(8), 707 (2020), https://doi.org/10.1001/jama.2020.0757.Suche in Google Scholar PubMed

[12] F. Esper, Z. Ou, Y. T. Huang. J. Clin. Virol. 48(2), 131 (2010), https://doi.org/10.1016/j.jcv.2010.03.007.Suche in Google Scholar PubMed PubMed Central

[13] World Health Organization, Coronavirus disease (COVID-19) pandemic, https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports (accessed May 1, 2020).Suche in Google Scholar

[14] World Health Organization (2020), Press conferences on COVID-19 and other global health issues, https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports (accessed April 16, 2020).Suche in Google Scholar

[15] E. Mahase. BMJ 368, m308 (2020), https://doi.org/10.1136/bmj.m308.Suche in Google Scholar PubMed

[16] Q. Li, X. Guan, P. Wu, X. Wang, L. Zhou, Y. Tong, Z. Feng. N. Engl. J. Med. 382, 1199 (2020), https://doi.org/10.1056/NEJMoa2001316.Suche in Google Scholar PubMed PubMed Central

[17] M. L. Holshue, C. DeBolt, S. Lindquist, K. H. Lofy, J. Wiesman, H. Bruce. N. Engl. J. Med. 382(10), 929 (2020), https://doi.org/10.1056/NEJMoa2001191.Suche in Google Scholar PubMed PubMed Central

[18] WHO, Coronavirus disease (COVID-19), https://www.who.int/news-room/q-a-detail/q-a-coronaviruses, https://www.cdc.gov/ (accessed May 1, 2020).Suche in Google Scholar

[19] Y. Wan, J. Shang, R. Graham, R. S. Baric, F. Li. J. Virol. 94, e00127 (2020), https://doi.org/10.1128/JVI.00127-20.Suche in Google Scholar PubMed PubMed Central

[20] J. A. Jaimes, J. K. Millet, A. E. Stout, N. M. Andre, G. R. Whittaker. Viruses 12(1), E83 (2020), https://doi.org/10.3390/v12010083.Suche in Google Scholar PubMed PubMed Central

[21] H. Lu. Biosci. Trends 14, 69 (2020), https://doi.org/10.5582/bst.2020.01020.Suche in Google Scholar PubMed

[22] N. Chen, M. Zhou, X. Dong, J. Qu, F. Gong, Y. Han. Lancet 395(10223), 507 (2020).10.1016/S0140-6736(20)30211-7Suche in Google Scholar PubMed PubMed Central

[23] M. Wang, R. Cao, L. Zhang, X. Yang, J. Liu, M. Xu. Cell Res. 30(3), 269 (2020), https://doi.org/10.1038/s41422-020-0282-0.Suche in Google Scholar PubMed PubMed Central

[24] M. Toots, J. J. Yoon, R. M. Cox, M. Hart, Z. M. Sticher, N. Makhsous. Sci. Transl. Med. 11, eaax5866 (2020), https://doi.org/10.1126/scitranslmed.aax5866.Suche in Google Scholar PubMed PubMed Central

[25] D. Siegel, M. Perron, R. Bannister, H. C. Hui, N. Larson, R. Strickley, J. Wells, K. S. Stuthman, S. A. Van Tongeren, N. L. Garza, G. Donnelly, A. C. Shurtleff, C. J. Retterer, D. Gharaibeh, R. Zamani, T. Kenny, B. P. Eaton, E. Grimes, L. S. Welch, L. Gomba, C. L. Wilhelmsen, D. K. Nichols, J. E. Nuss, E. R. Nagle, J. R. Kugelman, G. Palacios, E. Doerffler, S. Neville, E. Carra, M. O. Clarke, L. Zhang, W. Lew, B. Ross, Q. Wang, K. Chun, L. Wolfe, D. Babusis, Y. K. M. ParkStray, I. Trancheva, J. Y. Feng, O. Barauskas, Y. Xu, P. Wong, M. R. Braun, M. Flint, L. K. McMullan, S. S. Chen, R. Fearns, S. Swaminathan, D. L. Mayers, C. F. Spiropoulou, W. A. Lee, S. T. Nichol, T. Cihlar, S. Bavari. Nature 531(7594), 381 (2016), https://doi.org/10.1038/nature17180.Suche in Google Scholar PubMed PubMed Central

[26] S. R. Leist, K. Pyrc, J. Y. Feng, I. Trantcheva, R. Bannister, Y. Park, D. Babusis, M. O. Clarke, R. L. Mackman, J. E. Spahn, C. A. Palmiotti, D. Siegel, A. S. Ray, T. Cihlar, R. Jordan, M. R. Denison, R. S. Baric. Cell 183(4), 1070–1085.e12 (2017), https://doi.org/10.1016/j.cell.2020.09.050.Suche in Google Scholar PubMed PubMed Central

[27] T. P. Sheahan, A. C. Sims, R. L. Graham, V. D. Menachery, L. E. Gralinski, J. B. Case, S. R. Leist, K. Pyrc, J. Y. Feng, I. Trantcheva, R. Bannister. Sci. Transl. Med. 9(396), eaal3653 (2017), https://doi.org/10.1126/scitranslmed.aal3653.Suche in Google Scholar PubMed PubMed Central

[28] E. de Wit, F. Feldmann, J. Cronin, R. Jordan, A. Okumura, T. Thomas, D. Scott, T. Cihlar, H. Feldmann. Proc. Natl. Acad. Sci. 117, 6771 (2020), https://doi.org/10.1073/pnas.1922083117.Suche in Google Scholar PubMed PubMed Central

[29] FDA Approved Drugs Products: Hydroxychloroquine Oral Tablet, PLAQUENIL® HYDROXYCHLOROQUINE SULFATE TABLETS, USP instruction manual, www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s51lbl.pdf.Suche in Google Scholar

[30] S. Rampogu, M. R. Lemuel. BioMed Res. Int. 2016, 1–6 (2016), https://doi.org/10.1155/2016/6068437.Suche in Google Scholar PubMed PubMed Central

[31] B. Hu, Lill M. A.. J Comp Chem 35(16), 1255–1260 (2014), https://doi.org/10.1002/jcc.23616.Suche in Google Scholar PubMed PubMed Central

[32] D. Ghosh, J. Griswold, M. Erman, W. Pangborn. Nature 457(7226), 219 (2009), https://doi.org/10.1038/nature07614.Suche in Google Scholar PubMed PubMed Central

[33] J. Fei, L. Zhou, T. Liu, X. Y. Tang. Int. J. Med. Sci. 10(3), 265 (2013), https://doi.org/10.7150/ijms.5344.Suche in Google Scholar PubMed PubMed Central

[34] M. K. Abdel-Hamid, A. McCluskey. Molecules 19(5), 6609 (2014), https://doi.org/10.3390/molecules19056609.Suche in Google Scholar PubMed PubMed Central

[35] A. Fatima, A. B. H. Abdul, R. Abdullah, R. A. Karjiban, V. S. Lee. Int. J. Mol. Sci. 16(2), 2747 (2015), https://doi.org/10.3390/ijms16022747.Suche in Google Scholar PubMed PubMed Central

[36] N. K. Sharma, K. K. Jha, Priyanka. J. Adv. Sci. Res. 1, 67 (2010).Suche in Google Scholar

[37] A. M. Vijesh, A. M. Isloor, S. Telkar, T. Arulmoli, F. Hoong-Kun. Arab. J. Chem. 6, 197 (2013), https://doi.org/10.1016/j.arabjc.2011.10.007.Suche in Google Scholar

[38] R. Mishra, S. Mishra, J. Dash, J. Panigrahi. ChemRxiv (2020), https://doi.org/10.26434/chemrxiv.12646613.v2.Suche in Google Scholar

[39] D. Gfeller, A. Grosdidier, M. Wirth, A. Daina, O. Michielin, V. Zoete. Nucleic Acids Res. 42(W1), W32 (2014), https://doi.org/10.1093/nar/gku293.Suche in Google Scholar PubMed PubMed Central

[40] A. Daina, O. Michielin, V. Zoete. Nucleic Acids Res. 47(W1), W357 (2019), https://doi.org/10.1093/nar/gkz382.Suche in Google Scholar PubMed PubMed Central

[41] G. Wang, D. He, X. Li, J. Li, Z. Peng. Bioorg. Chem. 65, 167 (2016), https://doi.org/10.1016/j.bioorg.2016.03.001.Suche in Google Scholar PubMed

[42] I. H. R. Tomi, A. H. R. Al-Daraji, A. M. Abdula, M. F. Al-Marjani. J. Saudi Chem. Soc. 20, 509 (2016), https://doi.org/10.1016/j.jscs.2013.03.004.Suche in Google Scholar

[43] G. E. Kellogg, J. C. Burnett, D. J. Abraham. J. Comput. Aided Mol. Des. 15, 381 (2001), https://doi.org/10.1023/a:1011136228678.10.1023/A:1011136228678Suche in Google Scholar

[44] M. Zheng, Y. Lee, Y. Li, K. Hwangbo, C. Lee, J. Kim, J. Y. Son. Arch. Pharmacal Res. 9(33), 1307 (2010), https://doi.org/10.1007/s12272-010-0903-0.Suche in Google Scholar PubMed

[45] P. O. Widiakongko, D. Alisaputra, T. Kangkamano. Proceedings of the International Conference on Science and Engineering (ICSE-UIN-SUKA 2021) (2021).Suche in Google Scholar

[46] N. Malik, U. P. Dhuldhaj. Cell. Mol. Biomed. Rep. 1(3), 41 (2023), https://doi.org/10.55705/cmbr.2022.364739.1071.Suche in Google Scholar

[47] S. Mishra, R. Mishra, S. Dash, J. Panigrahi. ChemRxiv. (2020), https://doi.org/10.26434/chemrxiv.12646613.v2.Suche in Google Scholar

[48] S. Abubshait, H. Abubshait, R. R. Almalih, M. Gomaa, M. Nawaz, I. Ababutain, A. Alghamdi. Chemistryselect 7(46), 1–10 (2022), https://doi.org/10.1002/slct.202203925.Suche in Google Scholar

[49] W. JiaXu, B. Shao, J. Li, Z. Wang, M. Zhang, L. Jia, C. Ma. J. Agric. Food Chem. 71(33), 12462 (2023), https://doi.org/10.1021/acs.jafc.2c09148.Suche in Google Scholar PubMed

[50] Y. Aurora, I. Tarigan, N. Suryanto, P. Santosa, V. Pricillia, A. Parikesit. J. Fund. Appl. Sci. 18(6), 630 (2022), https://doi.org/10.11113/mjfas.v18n6.2594.Suche in Google Scholar

[51] A. Swargiary, M. Daimari. Sn Appl. Sci. 3(1), 36 (2021), https://doi.org/10.1007/s42452-020-04101-2.Suche in Google Scholar

[52] A. Tielens. Annu. Rev. Astron. Astrophys. 46, 289 (2008), https://doi.org/10.1146/annurev.astro.46.060407.145211.Suche in Google Scholar

[53] A. Boldyrev, L. Wang. Chem. Rev. 105(10), 3716 (2005), https://doi.org/10.1021/cr030091t.Suche in Google Scholar PubMed

[54] A. Shinozaki, K. Mimura, T. Nishida. Sci. Rep. 9, 7335 (2019), https://doi.org/10.1038/s41598-019-43868-2.Suche in Google Scholar PubMed PubMed Central

[55] Y. Zhang, P. Chen, Y. Ma, S. He, M. Liu. ACS Appl. Mater. Interfaces 1, 2036 (2009), https://doi.org/10.1021/am900399w.Suche in Google Scholar PubMed

Published Online: 2024-04-23
Published in Print: 2024-06-25

© 2024 IUPAC & De Gruyter

Artikel in diesem Heft

  1. Frontmatter
  2. In this issue
  3. Preface
  4. African Early Career Chemists Workshop & 8th Annual Symposium of the American Chemical Society, Nigeria International Chapter 2023
  5. Conference papers
  6. Design and simulation of 30 000 tons per year of cumene plant from natural gas field
  7. Activity profiling of natural and synthetic SARS-Cov-2 inhibitors using molecular docking analysis
  8. Efficiency of green synthesised carbon nanotubes from Moringa oleifera leaf extract as potential toxic metals adsorbent in polluted water
  9. Elucidating the interaction of FCC catalyst components: the discrete roles of matrix and binder on zeolite structure
  10. Coconut shell-derived green synthesised carbon nanotubes for clean-up of crude oil spills
  11. Electrodeposition behaviour of samarium in 1,3-dimethyl-2-imidazolidone solvent
  12. Special topic paper
  13. Importance of dielectric friction effect on polyelectrolytes conductivity
https://doi.org/10.1515/pac-2024-0012
Schlagwörter für diesen Artikel
8th Annual Symposium ACS Nigeria Chapter; ADMET; IUPAC African Early Career Chemists Workshop; COVID-19; flavonoid; hydroxychloroquine; macrocycles; nelfinavir; remdesivir; SARS-CoV-2

Artikel in diesem Heft

  1. Frontmatter
  2. In this issue
  3. Preface
  4. African Early Career Chemists Workshop & 8th Annual Symposium of the American Chemical Society, Nigeria International Chapter 2023
  5. Conference papers
  6. Design and simulation of 30 000 tons per year of cumene plant from natural gas field
  7. Activity profiling of natural and synthetic SARS-Cov-2 inhibitors using molecular docking analysis
  8. Efficiency of green synthesised carbon nanotubes from Moringa oleifera leaf extract as potential toxic metals adsorbent in polluted water
  9. Elucidating the interaction of FCC catalyst components: the discrete roles of matrix and binder on zeolite structure
  10. Coconut shell-derived green synthesised carbon nanotubes for clean-up of crude oil spills
  11. Electrodeposition behaviour of samarium in 1,3-dimethyl-2-imidazolidone solvent
  12. Special topic paper
  13. Importance of dielectric friction effect on polyelectrolytes conductivity
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