Open Access Peer-reviewed Research Article

Virtual screening as therapeutic strategy of COVID-19 targeting angiotensin-converting enzyme 2

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The protein complex structure
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Submitted   May 28, 2021
Published   Jun 16, 2021
Issue    Vol 2 No 1 (2021)
DOI   10.25082/FMI.2021.01.002

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Zahra Sharifinia
Department of Bioinformatics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Samira Asadi
Department of Bioinformatics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Mahyar Iranibazaz
Department of Bioinformatics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Abdollah Allahverdi corresponding author
Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Abstract

Objective: The receptor-binding domain (RBD) of the S1 domain of the SARS-CoV- 2 Spike protein performs a key role in the interaction with Angiotensin-converting enzyme 2 (ACE2), leading to both subsequent S2 domain-mediated membrane fusion and incorporation of viral RNA in host cells. Methods: In this study, we investigated the inhibitor’s targeted compounds through existing human ACE2 drugs to use as a future viral invasion. 54 FDA approved drugs were selected to assess their binding affinity to the ACE2 receptor. The structurebased methods via computational ones have been used for virtual screening of the best drugs from the drug database. Key Findings: The ligands “Cinacalcet” and “Levomefolic acid” highaffinity scores can be a potential drug preventing Spike protein of SARS-CoV-2 and human ACE2 interaction. Levomefolic acid from vitamin B family was proved to be a potential drug as a spike protein inhibitor in previous clinical and computational studies. Besides that, in this study, the capability of Levomefolic acid to avoid ACE2 and Spike protein of SARS-CoV-2 interaction is indicated. Therefore, it is worth to consider this drug for more in vitro investigations as ACE2 and Spike protein inhibition candidate. Conclusion: The two Cinacalcet and Levomefolic acid are the two ligands that have highest energy binding for human ACE2 blocking among 54 FDA approved drugs.

Keywords
SARS-CoV-2, COVID-19, ACE2 inhibitor, docking VINA, docking SMINA

Article Details

Supporting Agencies
The authors are thankful for funding from Iran National Science Foundation (INSF) Grant No. 96006759.
How to Cite
Sharifinia, Z., Asadi, S., Iranibazaz, M., & Allahverdi, A. (2021). Virtual screening as therapeutic strategy of COVID-19 targeting angiotensin-converting enzyme 2. Frontiers in Molecular Immunology, 2(1), 16-26. https://doi.org/10.25082/FMI.2021.01.002
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

References

  1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 2020, 395(10223): 497-506. https://doi.org/10.1016/S0140-6736(20)30183-5
  2. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798): 270-273. https://doi.org/10.1038/s41586-020-2012-7
  3. Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circulation Research, 2000, 87(5): e1-9. https://doi.org/10.1161/01.RES.87.5.e1
  4. Souza S, Oliveira SW, Alzamora AC, et al. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin- Angiotensin System: Focus on Angiotensin-(1-7). Physiological Reviews, 2018, 98(1): 505. https://doi.org/10.1152/physrev.00023.2016
  5. Bohm HJ. Protein-Ligand Interactions: From Molecular Recognition to Drug Design. Edited by B¨ohm HJ and Schneider G, 2003.
  6. Veeramachaneni GK, Thunuguntla V, Janaki RB, et al. Structural and Simulation analysis of hot spot residues interactions of SARS-CoV 2 with Human ACE2 receptor. Journal of biomolecular Structure & Dynamics, 2020: 1-11. https://doi.org/10.1080/07391102.2020.1773318
  7. Hasan A, Paray BA, Hussain A, et al. A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin. Journal of biomolecular Structure & Dynamics, 2021, 39(8): 3025-3033. https://doi.org/10.1080/07391102.2020.1754293
  8. Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science, 2020, 367(6485): eabb2762. https://doi.org/10.1126/science.abb2762
  9. Boopathi S, Poma AB and Kolandaivel P. Novel 2019 Coronavirus Structure, Mechanism of Action, Antiviral drug promises and rule out against its treatment. Journal of biomolecular Structure & Dynamics, 2020: 1-14. https://doi.org/10.1080/07391102.2020.1758788
  10. Trezza A, Iovinelli D, Santucci A, et al. An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors. Scientific Reports, 2020, 10(1): 13866. https://doi.org/10.1038/s41598-020-70863-9
  11. Ho TY, Wu SL, Chen JC, et al. Design and biological activities of novel inhibitory peptides for SARS-CoV spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Research, 2006, 69(2): 70-76. https://doi.org/10.1016/j.antiviral.2005.10.005
  12. Fang L, Karakiulakis G and Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? The Lancet Respiratory Medicine, 2020, 8(4): e21. https://doi.org/10.1016/S2213-2600(20)30116-8
  13. Bunyavanich S, Do A and Vicencio A. Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults. JAMA - Journal of the American Medical Association, 2020, 323(23): 2427-2429. https://doi.org/10.1001/jama.2020.8707
  14. Adeoye AO, Oso BJ, Olaoye IF, et al. Repurposing of chloroquine and some clinically approved antiviral drugs as effective therapeutics to prevent cellular entry and replication of coronavirus. Journal of biomolecular Structure & Dynamics, 2020: 1-11. https://doi.org/10.1080/07391102.2020.1765876
  15. Trott O and Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 2010, 31(2): 455-461. https://doi.org/10.1002/jcc.21334
  16. Koes DR, Baumgartner MP and Camacho CJ. Downloaded via Academy of Sciences Czech Republic on January 6. J. Chem. Inf. Model, 2013.
  17. Hussain M, Jabeen N, Raza F, et al. Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein. Journal of medical virology, 2020, 92(9): 1580-1586. https://doi.org/10.1002/jmv.25832
  18. Sama IE, Ravera A, Santema BT, et al. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors. European Heart Journal, 2020, 41(19): 1810-1817. https://doi.org/10.1093/eurheartj/ehaa373
  19. Zu Y, Lu X, Song J, et al. Cinacalcet Treatment Significantly Improves All-Cause and Cardiovascular Survival in Dialysis Patients: Results from a Meta-Analysis. Kidney and Blood Pressure Research, 2019, 44(6): 1-12. https://doi.org/10.1159/000504139
  20. Block GA, Martin KJ, De Francisco ALM, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. New England Journal of Medicine, 2004, 350(15): 1516-1525. https://doi.org/10.1056/NEJMoa031633
  21. Gillespi IA, Floege J, Gioni I, et al. Propensity score matching and persistence correction to reduce bias in comparative effectiveness: the effect of cinacalcet use on all-cause mortality. Pharmacoepidemiology and Drug Safety, 2015, 24(7): 738-747. https://doi.org/10.1002/pds.3789
  22. Edward I, Yishay W, Amitai S, et al. Clinical Characterization of 162 COVID-19 patients in Israel: Preliminary Report from a Large Tertiary Center. The Israel Medical Association Journal, 2020, 22(5): 271-274.
  23. Liakishev AA. Homocysteine lowering with folic acid and B vitamins in vascular disease. Kardiologiia, 2006, 44(3): 684-684. https://doi.org/10.1016/j.jvs.2006.07.009
  24. Rydlewicz A, Simpson JA, Taylor RJ, et al. The effect of folic acid supplementation on plasma homocysteine in an elderly population. Qjm, 2002, 95(1): 27-35. https://doi.org/10.1093/qjmed/95.1.27
  25. Serseg T, Benarous K and Yousfi M. Hispidin and Lepidine E: two Natural Compounds and Folic acid as Potential Inhibitors of 2019-novel coronavirus Main Protease (2019-nCoVMpro), molecular docking and SAR study. arXiv, 2020: 1-13. https://doi.org/10.13140/RG.2.2.21925.86247/1
  26. Kumar A, Sharanya CS, Sadasivan C, et al. Drug Repurposing to Identify Therapeutics Against COVID 19 with SARS-Cov-2 Spike Glycoprotein and Main Protease as Targets: An in Silico Study, 2020. https://doi.org/10.26434/chemrxiv.12090408.v1
  27. Prajapat M, Shekhar N, Sarma P, et al. Virtual screening and molecular dynamics study of approved drugs as inhibitors of spike protein S1 domain and ACE2 interaction in SARS-CoV-2. Journal of Molecular Graphics and Modelling, 2020, 101: 107716. https://doi.org/10.1016/j.jmgm.2020.107716
  28. Choudhary S, Malik YS and Tomar S. Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. Frontiers in Immunology, 2020, 11: 1664. https://doi.org/10.3389/fimmu.2020.01664
  29. Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nature Medicine, 2005, 11(8): 875. https://doi.org/10.1038/nm1267
  30. Benarba B and Pandiella A. Medicinal Plants as Sources of Active Molecules Against COVID-19. Frontiers in Pharmacology, 2020, 11: 1189. https://doi.org/10.3389/fphar.2020.01189
  31. Li S, Hao X, Xiao S, et al. The Effect of YiQiFuMai on Ischemic Heart Failure by Improve Myocardial Microcirculation and Increase eNOS and VEGF Expression. International Journal of Clinical Medicine, 2020, 11(2): 84-100. https://doi.org/10.4236/ijcm.2020.112009
  32. Niu M, Wang RL, Wang ZX, et al. Rapid establishment of traditional Chinese medicine prevention and treatment of 2019-nCoV based on clinical experience and molecular docking. China journal of Chinese materia medica, 2020, 45(6): 1213-1218. https://doi.org/10.19540/j.cnki.cjcmm.20200206.501
  33. Zou X, Chen K, Zou J, et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Frontiers of Medicine, 2020, 14: 185-192. https://doi.org/10.1007/s11684-020-0754-0
  34. Li SR, Tang ZJ, Li ZH, et al. Searching therapeutic strategy of new coronavirus pneumonia from angiotensin-converting enzyme 2: the target of COVID-19 and SARS-CoV. European Journal of Clinical Microbiology & Infectious Diseases, 2020, 39: 1021-1026. https://doi.org/10.1007/s10096-020-03883-y
  35. Rahman MM, Saha T, Islam KJ, et al. Virtual screening, molecular dynamics and structure-activity relationship studies to identify potent approved drugs for Covid-19 treatment. Journal of biomolecular Structure & Dynamics, 2020: 1-11. https://doi.org/10.1080/07391102.2020.1794974
  36. Cagno V, Magliocco G, Tapparel C, et al. The tyrosine kinase inhibitor nilotinib inhibits SARS-CoV-2 in vitro. Basic & Clinical Pharmacology & Toxicology, 2020, 128(4): 621-624. https://doi.org/10.1111/bcpt.13537