In Silico Inhibition Potential of Artemisinin Derivatives Against SARS-CoV-2 Main Protease

Year 2021, Volume: 8 Issue: 2, 809 - 816, 31.05.2021

Mustafa Emirik

https://doi.org/10.31202/ecjse.894617

Cited By: 1

Abstract

The outbreak of COVID-19 caused by the SARS-CoV-2 virus has recently become a pandemic and affected millions worldwide. The natural compounds obtained from medicinal plants have been proven to be the source of many treatments throughout history. Efforts to combat Sars-CoV-2 generally focused on repositioning drugs or finding treatments with natural compounds and have been rapidly ongoing. Main protease (Mpro) is a vital protein of SARS-CoV-2 and an important target of drug research. The present study evaluated seven artemisinin derivatives: Artemisinin, Artemether, Arteether, Artesunate, Dihydroartemisinic acid Dihydroartemisinin and Artemisinic Acid. For this purpose, the molecular docking study was carried out to investigate the potency of artemisinin derivatives against the SARS-CoV-2 Mpro. As a result, Artesunate, Dihydroartemisinic acid and dihydroartemisinin had promising results in Mpro inhibition with the binding energies between -8.42 and -9.35 kcal/mol.

Keywords

Artesunate, Artemisinin, Covid-19, Main Protease

Thanks

The numerical calculations reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance, and Grid Computing Center (TRUBA resources).

Artemisinin Türevi Bileşiklerin Sars-CoV-2 Ana Proteaz Proteinine Karşı In Silico İnhibisyon Potansiyeli

Abstract

SARS-CoV-2 virüsünün neden olduğu COVID-19 salgını son zamanlarda bir salgın haline geldi ve dünya çapında milyonlarca insanı etkiledi. Şifalı bitkilerden elde edilen doğal bileşiklerin, tarih boyunca birçok tedavinin kaynağı olduğu kanıtlanmıştır. Sars-CoV-2 ile mücadele çabaları genellikle ilaçları yeniden konumlandırmaya veya doğal bileşiklerle tedaviler bulmaya odaklandı ve hızla devam ediyor. Ana proteaz (Mpro), SARS-CoV-2'nin hayati bir proteinidir ve ilaç araştırmalarının önemli bir hedefidir. Bu çalışmada, Artemisinin, Artemether, Arteether, Artesunate, Dihydroartemisinic acid, Dihydroartemisinin ve Artemisinic Acid olmak üzere 7 artemisinin türevinin değerlendirilmesi amaçlanmıştır. Bu amaçla, artemisinin türevlerinin SARS-CoV-2 Mpro'ya karşı potansiyelini araştırmak için Moleküler Docking çalışması yapılmıştır. Sonuçta Artesunate, Dihydroartemisinic acid ve Dihydroartemisinin, -8.42 ile -9.35 kcal/mol arasında bağlanma enerjisi ile Mpro inhibisyonu açısından umut verici sonuçlar ortaya çıkarmıştır.

Keywords

Artemisinin, Artesunate, Covid-19, Main protease

References

• Referans1. Emirik, M. Potential therapeutic effect of turmeric contents against SARS-CoV-2 compared with experimental COVID-19 therapies: in silico study. J. Biomol. Struct. Dyn. 2020, doi:10.1080/07391102.2020.1835719.
• Referans2. Islam, M.T.; Sarkar, C.; El-Kersh, D.M.; Jamaddar, S.; Uddin, S.J.; Shilpi, J.A.; Mubarak, M.S. Natural products and their derivatives against coronavirus: A review of the non-clinical and pre-clinical data. Phyther. Res. 2020, 34, 2471–2492, doi:10.1002/ptr.6700.
• Referans3. Wangkheirakpam, S. Traditional and Folk Medicine as a Target for Drug Discovery. In; Mandal, S.C., Mandal, V., Konishi, T.B.T.-N.P. and D.D., Eds.; Elsevier, 2018; pp. 29–56 ISBN 978-0-08-102081-4.
• Referans4. Ganjhu, R.K.; Mudgal, P.P.; Maity, H.; Dowarha, D.; Devadiga, S.; Nag, S.; Arunkumar, G. Herbal plants and plant preparations as remedial approach for viral diseases. VirusDisease 2015, 26, 225–236, doi:10.1007/s13337-015-0276-6.
• Referans5. Akbaş, M.N.; Akçakaya, A. COVID-19 ve Fitoterapi. Bezmialem Sci. 2020, 8, 428–437, doi:10.14235/bas.galenos.2020.4962.
• Referans6. Din, M.; Ali, F.; Waris, A.; Zia, F.; Ali, M. Phytotherapeutic options for the treatment of COVID-19: A concise viewpoint. Phyther. Res. 2020, 34, 2431–2437, doi:10.1002/ptr.6786.
• Referans7. Antonelli, M.; Donelli, D.; Maggini, V.; Firenzuoli, F. Phytotherapic compounds against coronaviruses: Possible streams for future research. Phyther. Res. 2020, 34, 1469–1470, doi:10.1002/ptr.6712.
• Referans8. Boozari, M.; Hosseinzadeh, H. Natural products for COVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies. Phyther. Res. 2020, 1–13, doi:10.1002/ptr.6873.
• Referans9. Derosa, G.; Maffioli, P.; D’Angelo, A.; Di Pierro, F. A role for quercetin in coronavirus disease 2019 (COVID-19). Phyther. Res. 2020, 1–7, doi:10.1002/ptr.6887.
• Referans10. Rahman, F.; Tabrez, S.; Ali, R.; Alqahtani, A.S.; Ahmed, M.Z.; Rub, A. Journal of Traditional and Complementary Medicine Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins. J. Tradit. Chinese Med. Sci. 2021, 11, 173–179, doi:10.1016/j.jtcme.2021.01.006.
• Referans11. Scavone, C.; Brusco, S.; Bertini, M.; Sportiello, L.; Rafaniello, C.; Zoccoli, A.; Berrino, L.; Racagni, G.; Rossi, F.; Capuano, A. Current pharmacological treatments for COVID-19: What’s next? Br. J. Pharmacol. 2020, 177, 4813–4824, doi:10.1111/bph.15072.
• Referans12. Singh, E.; Khan, R.J.; Jha, R.K.; Amera, G.M.; Jain, M.; Singh, R.P.; Muthukumaran, J.; Singh, A.K. A comprehensive review on promising anti-viral therapeutic candidates identified against main protease from SARS-CoV-2 through various computational methods. J. Genet. Eng. Biotechnol. 2020, 18, doi:10.1186/s43141-020-00085-z.
• Referans13. Boras, B.; Jones, R.M.; Anson, B.J.; Arenson, D.; Aschenbrenner, L.; Bakowski, M.A.; Beutler, N.; Binder, J.; Chen, E.; Eng, H.; et al. Discovery of a Novel Inhibitor of Coronavirus 3CL Protease as a Clinical Candidate for the Potential Treatment of COVID-19. bioRxiv Prepr. Serv. Biol. 2020, doi:10.1101/2020.09.12.293498.
• Referans14. Qu, J.; Li, G.; Wang, J.; Huang, G.H.J.; Chen, Y.; Qu, Q.; Qiong, X.C. Comparative effectiveness of Lopinavir / Ritonavir-based regimens in COVID-19. 2021, 203–210, doi:10.1111/1440-1681.13425.
• Referans15. Tahir ul Qamar, M.; Alqahtani, S.M.; Alamri, M.A.; Chen, L.L. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. J. Pharm. Anal. 2020, 10, 313–319, doi:10.1016/j.jpha.2020.03.009.
• Referans16. Yang, H.; Yang, M.; Ding, Y.; Liu, Y.; Lou, Z.; Zhou, Z.; Sun, L.; Mo, L.; Ye, S.; Pang, H.; et al. The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 13190–13195, doi:10.1073/pnas.1835675100.
• Referans17. Sehailia, M.; Chemat, S. Antimalarial-agent artemisinin and derivatives portray more potent binding to Lys353 and Lys31-binding hotspots of SARS-CoV-2 spike protein than hydroxychloroquine: potential repurposing of artenimol for COVID-19. J. Biomol. Struct. Dyn. 2020, 0, 1–11, doi:10.1080/07391102.2020.1796809.
• Referans18. Haq, F.U.; Roman, M.; Ahmad, K.; Rahman, S.U.; Shah, S.M.A.; Suleman, N.; Ullah, S.; Ahmad, I.; Ullah, W. Artemisia annua: Trials are needed for COVID-19. Phyther. Res. 2020, 34, 2423–2424, doi:10.1002/ptr.6733.
• Referans19. Castilho, P.C.; Gouveia, S.C.; Rodrigues, A.I. Quantification of artemisinin in Artemisia annua extracts by 1H-NMR. Phytochem. Anal. 2008, 19, 329–334, doi:10.1002/pca.1053.
• Referans20. D’alessandro, S.; Scaccabarozzi, D.; Signorini, L.; Perego, F.; Ilboudo, D.P.; Ferrante, P.; Delbue, S. The use of antimalarial drugs against viral infection. Microorganisms 2020, 8, 1–26, doi:10.3390/microorganisms8010085.
• Referans21. Gendrot, M.; Duflot, I.; Boxberger, M.; Delandre, O.; Jardot, P.; Le Bideau, M.; Andreani, J.; Fonta, I.; Mosnier, J.; Rolland, C.; et al. Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: In vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate. Int. J. Infect. Dis. 2020, 99, 437–440, doi:10.1016/j.ijid.2020.08.032.
• Referans22. Schrödinger Release 2018-4: Maestro, Schrödinger, LLC 2018.
• Referans23. Salentin, S.; Schreiber, S.; Haupt, V.J.; Adasme, M.F.; Schroeder, M. PLIP: Fully automated protein-ligand interaction profiler. Nucleic Acids Res. 2015, 43, W443–W447, doi:10.1093/nar/gkv315.
• Referans24. Jin, Z.; Du, X.; Xu, Y.; Deng, Y.; Liu, M.; Zhao, Y.; Zhang, B.; Li, X.; Zhang, L.; Peng, C.; et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 2020, 582, 289–293, doi:10.1038/s41586-020-2223-y.
• Referans25. Schrödinger Release 2018-4: Protein Preparation Wizard; Epik, Schrödinger, LLC, New York, NY, 2016; Impact, Schrödinger, LLC, New York, NY, 2016; Prime, Schrödinger, LLC, New York, NY, 2018.
• Referans26. Schrödinger Release 2018-1: Induced Fit Docking protocol; Glide, Schrödinger, LLC, New York, NY, 2016; Prime, Schrödinger, LLC 2018.
• Referans27. Harder, E.; Damm, W.; Maple, J.; Wu, C.; Reboul, M.; Xiang, J.Y.; Wang, L.; Lupyan, D.; Dahlgren, M.K.; Knight, J.L.; et al. OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins. J. Chem. Theory Comput. 2016, 12, 281–296, doi:10.1021/acs.jctc.5b00864.
• Referans28. Jacobson, M.P.; Pincus, D.L.; Rapp, C.S.; Day, T.J.F.; Honig, B.; Shaw, D.E.; Friesner, R.A. “A Hierarchical Approach to All-Atom Protein Loop Prediction,.” Proteins Struct. Funct. Bioinforma. 2004, 55, 351–367.