In Silico Study for Similar FDA Approved Drugs as Inhibitors of SARS-CoV-2 Spike and the Host Receptor Proteins
DOI:
https://doi.org/10.33084/jmd.v1i2.2213Keywords:
Molecular docking, SARS-CoV-2, spike protein, ACE2 receptor, 14-ketostypodiol diacetateAbstract
The severe acute respiratory syndrome coronavirus 2, known as COVID-19, has been hideously increased worldwide. The disease began in Wuhan, China, around December 2019, then spread to most countries. Social distancing is the best procedure to prevent infection. Screening the available database containing millions of drug molecules or phytochemicals has become rapid and straightforward because of the computer-aided drug design (CADD) methods. In the present study, 300 phytochemicals and cellulose ether derivatives are screened through a docking study. Docking analysis showed that only four molecules (a-neohesperidin, quercetin 3-O-glucosylrutinoside, 14-ketostypodiol diacetate, and hydroxypropyl methylcellulose) were able to interact with the spike protein. However, two among them (quercetin 3-O-glucosylrutinoside and 14-ketostypodiol diacetate) could interact with the host cell receptor (ACE2) of SARS-CoV-2. The binding affinity of the four compounds is high. Still, according to Lipinski's rule of five, only 14-ketostypodiol diacetate was selected as a drug molecule due to its pharmacokinetic and ADMET properties. Screening for drug analogs to the 14-ketostypodiol diacetate detected five approved drugs. Docking analysis of these drugs with the target proteins showed that the five drugs interact with the host receptor protein, and three interact with viral spike protein. Accordingly, we suggest that molecular docking and drug analogs studies could support rapid drug development. In addition, future perspectives on therapeutic applications of 14-ketostypodiol diacetate are required for using it against SARS-CoV-2 infections.
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References
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7. Xia X. Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design. Viruses. 2021;13(1):109. doi:10.3390/v13010109
8. Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41:1141-9. doi:10.1038/s41401-020-0485-4
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10. Tortorici MA, Veesler D. Structural insights into coronavirus entry. Adv Virus Res. 2019;105:93-116. doi:10.1016/bs.aivir.2019.08.002
11. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367(6485):1444-8. doi:10.1126/science.abb2762
12. Ibrahim IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-19 spike-host cell receptor GRP78 binding site prediction. J Infect. 2020;80(5):554-62. doi:10.1016/j.jinf.2020.02.026
13. Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, et al. Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases. ACS Cent Sci. 2020;6(3):315-31. doi:10.1021/acscentsci.0c00272
14. Ma L, Li H, Lan J, Hao X, Liu H, Wang X, et al. Comprehensive analyses of bioinformatics applications in the fight against COVID-19 pandemic. Comput Biol Chem. 2021;95:107599. doi:10.1016/j.compbiolchem.2021.107599
15. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260-3. doi:10.1126/science.abb2507
16. Gui M, Song W, Zhou H, Xu J, Chen S, Xiang Y, et al. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. 2017;27(1):119-29. doi:10.1038/cr.2016.152
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22. Tallei TE, Tumilaar SG, Niode NJ, Fatimawali, Kepel BJ, Idroes R, et al. Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (M pro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study. Scientifica. 2020;2020:6307457. doi:10.1155/2020/6307457
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28. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5(4):562-9. doi:10.1038/s41564-020-0688-y
29. Desai NC, Kotadiya GM, Trivedi. Studies on molecular properties prediction, antitubercular and antimicrobial activities of novel quinoline based pyrimidine motifs. Bioorg Med Chem Lett. 2014;24(14):3126-30. doi:10.1016/j.bmcl.2014.05.002
30. Ming Y, Qiang L. Involvement of Spike Protein, Furin, and ACE2 in SARS-CoV-2-Related Cardiovascular Complications. SN Compr Clin Med. 2020;Online ahead of print. doi:10.1007/s42399-020-00400-2
31. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45(12):2615-23. doi:10.1021/jm020017n
32. Purandare AV. Understanding Drug Development: A Primer on the Food and Drug Administration. J Pediatric Infect Dis Soc. 2021;10(10):977-81. doi:10.1093/jpids/piab023
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Published
2021-12-30
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Shamkh IM, Pratiwi D, Omar HS, Reyad NE-HA. In Silico Study for Similar FDA Approved Drugs as Inhibitors of SARS-CoV-2 Spike and the Host Receptor Proteins. J Mol Docking [Internet]. 2021Dec.30 [cited 2024Nov.15];1(2):49-58. Available from: https://journal.umpr.ac.id/index.php/jmd/article/view/2213
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