In silico Study on Physicochemical, Pharmacokinetic and Toxicity Profiles of Available Antiviral Drugs and The Drug-Target Interaction with Protease of SARS-CoV-2
Artikel Sidebar
-
ADMET, antiviral drugs, in silico, physicochemical, SARS-CoV-2
Abstrak
Introduction: In emergency conditions such as the COVID-19 pandemic, many drugs treating SARS-CoV-2 are currently being developed through the concept of repurposing the existing drugs. This study aims to evaluate the physicochemical, pharmacokinetic and toxicity (ADMET) profiles of 15 drugs that have been used clinically for other viral diseases, and inspect their activity as antivirals against SARS-CoV-2. Methods: The physicochemical properties were obtained by using the ChemDraw and the ADMET were predicted using pkCSM on line tools. The selected drugs based on Lipinski's Rules were docked into main protease of SARS-CoV-2 (PDB. 6LU7) using Molegro program. Results: Six drugs complied with Lipinski's Rules and showed good ADMET profile except for their hepatotoxicity, but favipiravir and oseltamivir were predicted to be non-hepatotoxic. Oseltamivir also showed high binding affinity with free energy score below -100 kcal/mol. Conclusions: Oseltamivir is a potential antivirus for COVID-19 based on physicochemical, ADMET profile, and in silico activity against protease of SARS-CoV-2.
Â
Artikel teks lengkap
Referensi
Acosta, P.E., (2018). Antiviral agents (nonretroviral). In L.L. Brunton, R. Hilal-Dandan, B.J. Knollmann (Eds). Goodman & Gilman’s the pharmacological basis of therapeutics 13th ed. (pp. 1105–1116). McGraw-Hill Education, New York.
BPOM Republic of Indonesia (National Agency of Drug and Food Control). (2014). Peraturan Kepala Badan Pengawas Obat dan Makanan Republik Indonesia No. 7 tahun 2014 tentang Pedoman Uji Toksisitas Nonklinik Secara In Vivo.
Cai, Q., Yang, M., Liu, D., Chen J., Shu, D., Xia, J., Liao, X., Gu, Y., Cai, Q., Yang, Y., Shen, C., Li, X., Peng, L., Huang, D., Zhang, J., Zhang, S., Wang, F., et al. (2020). Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering, 6(10): 1192-1198. https://doi.org/10.1016/j.eng.2020.03.007
Chen, J., Xia, L., Liu, L., Xu, Q., Ling, Y., Huang, D., Huang, W., Song, S., Xu, S., Shen, Y., and Lu, H. (2020). Antiviral Activity and Safety of Darunavir/Cobicistat for the Treatment of COVID-19. Open Forum Infectious Diseases: 1-5. http://doi.org/ 10.1093/ofid/ofaa241
Chhikara, B. S., Rathi, B., Singh, J., & Poonam, F. N. U. (2020). Corona virus SARS-CoV-2 disease COVID-19: Infection, prevention and clinical advances of the prospective chemical drug therapeutics. Chemical Biology Letters, 7(1), 63–72. http://pubs. iscience.in/ journal/index.php/cbl/article/view/995
Chu, C.M., Cheng, V.C.C., Hung, I.F.N., Wong, M.M.L., Chan, K.H., Chan, K.S., Kao, R.Y.T., Poon, L.L.M., Wong, C.L.P., Guan, Y., Peiris, J.S.M., Yuen, K.Y. (2004). Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax, 59:252-256. http://doi.org/10.1136/thorax.2003.012658
Cui, W., Yang, K., Haitao Yang, H. (2020). Recent Progress in the Drug Development Targeting SARS-CoV-2 Main Protease as Treatment for COVID-19. Frontiers in Molecular Biosciences 7:1–10. https://doi.org/10.3389/fmolb.2020.616341
Delang, L., Abdelnabi, R., Neyts, J., Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. (2018). Antiviral Resesearch, 153:85-94. https://doi.org/ 10.1016/j.antiviral.2018.03.003
Dong, L., Hu, S., Gao, J. (2020). Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discoveries & Therapeutics, 14(1):58-60. https://doi.org/10.5582/ddt. 2020.01012
Dou, D., Revol, R., Östbye, H., Wang, H., Daniels, R. (2018). Influenza A virus cell entry, replication, virion assembly and movement. Front Immunology, 20(9):1581. http://doi.org/10.3389/fimmu.2018.01581
Fehr, A.R., Perlman S. (2015) Coronaviruses: an overview of their replication and pathogenesis. Methods Molecular Biology,1282:1–23. http://doi.org/10.1007/978-1-4939-2438-7_1
Formiga, F.R., L., De Souza, J., Paiva, L. (2020). Ivermectin: an award-winning drug with expected antiviral activity against COVID-19. Journal of Controlled Release, 10(329): 758–761. http://doi.org/10.1016/j.jconrel.2020.10.009
Haviernik, J., Å tefánik, M., FojtÃková, M., Kali, S., Rudolf, I., Hubálek, Z., Eyer, L., Ruzek, D., Tordo, N. (2018). Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses. Viruses, 10(184): 1-8. http://doi.org/ 10.3390/v10040184
Indu, P., Rameshkumar, M.R., Arunagirinathana, N., Al-Dhabi, N.A., Mariadhas Valan Arasud, M.V., Ignacimuthu, S. (2020). Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach. Journal of Infection and Public Health, 13(12):1856–1861. http://doi.org/10.1016/j.jiph.2020.10.015
Joshi, R.S., Jagdale, S.S., Bansode, S.B., Shankar, S.S., Tellis, M.B., Pandya, V.K., Chugh, A., Giri, A.P., Kulkarni, M.J.. (2021). Discovery of Potential Multi-Target-Directed Ligands by Targeting Host-Specific SARS-CoV-2 Structurally Conserved Main Protease. Journal of Biomolecular Structure and Dynamics, 39(9):3099-3114. https://doi.org/ 10.1080/07391102.2020.1760137.
Li, G., De Clercq, E. (2020). Therapeutic options for the 2019 novel coronavirus (2019-nCoV) Nature reviews Drug Discovery,19:149-150. https://doi.org/10.1038/d41573-020-00016-0
Lipinski, C. A., Lombardo, F., Dominy, B.W., Feeney, P.J. (2012). Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Advanced Drug Delivery Reviews 64(SUPPL.):4–17. http://doi.org/10.1016/s0169-409x(00)00129-0
Lou, Y., Liu, L., Yao, H., Hu, X., Su, J., Xu, K., Luo, R., He, L., Lu, X., Zhao, Q., Liang, T., Qiu, Y., First, T., (2020). Clinical Outcomes and Plasma Concentrations of Baloxavir Marboxil and Favipiravir in COVID-19 Patients: An Exploratory Randomized, Controlled Trial. European Journal of Pharmaceutical Sciences, 157:105631. https://doi.org/10.1016/j.ejps.2020.105631.
Mercorelli, B., Palù, G., Arianna Loregian, A. (2018). Drug Repurposing for Viral Infectious Diseases: How Far Are We? Trends in Microbiology, 26(10): 865–876.
Musarrat, F., Chouljenko, V., Dahal, A., Nabi, R., Chouljenko, T., Jois, S.D., Kousoulas, K.G. (2020). The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections. Journal of Medical Virology: 1-9. http://doi.org/10.1002/jmv.25985
Pathak, Y., Mishra, A., Choudhir, G., Kumar, A., Tripathi, V. (2021). Rifampicin and Letermovir as potential repurposed drug candidate for COVID-19 treatment: insights from an in-silico study. Pharmacological Reports, 1-13. https://doi.org/10.1007/s43440-021-00228-0
Quimque, M. T. J., Notarte, K. I. R., Fernandez, R. A. T., Mendoza, M. A. O., Liman, R. A. D., Lim, J. A. K., Wei, D. Q. (2020). Virtual Screening-Driven Drug Discovery of SARS-CoV2 Enzyme Inhibitors Targeting Viral Attachment, Replication, Post-Translational Modification and Host Immunity Evasion Infection Mechanisms. Journal of Biomolecular Structure and Dynamics, 39(12): 4316–4333. http://doi.org/ 10.1080/07391102.2020.1776639. 39(12):4316-4333
Reznik, S.E., Tiwari, A.K., Ashby, C.R. (2018). Sofosbuvir: A Potential Treatment for Ebola. Frontiers in Pharmacology, 9: 2016–2019.
Safrin, S. (2009). Antiviral Agents. In B.G. Katzung, S. Masters, A.J. Trevor (Eds), Basic and Clinical Pharmacology 11th ed. (pp. 853-857). McGraw Hill Medical, New York.
Sisk, J.M., Frieman, M.B., Machamer, C.E. (2018). Coronavirus S Protein-Induced Fusion Is Blocked Prior to Hemifusion by Abl Kinase Inhibitors. Journal of General Virology, 99(5): 619–630.
Rizzo, E. (2020). Ivermectin, Antiviral Properties and COVID-19: A Possible New Mechanism of Action. Naunyn-Schmiedeberg’s Archives of Pharmacology, 393(7):1153–1156. http://doi.org/10.1007/s00210-020-01902-5
Ullrich, S., and Nitsche, C. (2020). The SARS-CoV-2 main protease as drug target. Bioorganic & Medicinal Chemistry Letters, 30:127377. https://doi.org/10.1016/j.bmcl.2020.127377
Vankadari,N. (2020). Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein. International Journal of Antimicrobial Agents, 56:105998. https://doi.org/10.1016/j.ijantimicag.2020.105998
Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., et al. (2019). Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 323(11):1061–1069. http://doi.org/10.1001/jama.2020.1585
Wang, Z, Chen X, Lu Y, Chen, F., Zhang, W.(2020). Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Bioscience Trends, 14:64–68. http:// doi.org/10.5582/bst.2020.01030
Wu, R., Wang, L., Kuo, H-C.D., Shannar, A., Peter, R., Chou, P.J., Li, S., Hudlikar, R., et al. (2020). An Update on Current Therapeutic Drugs Treating COVID-19. Current Pharmacology Reports, 11: 1–15. https://doi.org/10.1007/s40495-020-00216-7.
Wu, X., Cai, Y., Huang, X., Yu, X., Zhao, L., Wang F., et.al. Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China. (2020) Emerging Infectious Disease, 26(6):1324–1326. http://doi.org/10.3201/eid2606.200299
Yilmaz, H., Guner, E., Altuntas, M. (2020). Results of Favipiravir Combined Treatment in Intensive Care Patients With Covid-19. Research Square, 1-11. https://doi.org/ 10.21203/rs.3.rs-132216/v1
Penulis
Penulis tetap memegang hak atas karyanya dan memberikan hak publikasi pertama kepada jurnal ini yang secara simultan karya tersebut dilisensikan di bawah: Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)