Research Article
Evaluation of Receptor Relationships of Some Drugs Used in the Treatment of COVID-19 by Modeling Studies
Abstract
Objective: It is important to investigate the interactions of drugs used in the treatment process of COVID-19 with cellular mechanisms. In this study, the aim was to investigate the interactions of Dexamethasone, Favipiravir, and Hydroxychloroquine drugs used in the treatment of COVID-19 with the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2).
Materials and Methods: Within the scope of the study, firstly, 3-dimensional structures of receptors and drug molecules were formed. Then the interactions of each of the receptor and drug molecules at the binding site were examined by molecular docking studies, which is a computer-aided drug design method, and their binding affinities were evaluated.
Results: As a result of the analyses, it was determined that the drug named Hydroxychloroquine has the highest and the drug called Dexamethasone has the lowest binding affinity for all three receptors. In addition, it has been determined that Dexamethasone develops inappropriate interactions with ER and HER2 receptor active site amino acids.
Conclusions: In this study, preliminary data on how receptor interactions can occur when normal individuals and breast cancer patients use Dexamethasone, Favipiravir, and Hydroxychloroquine are presented.
References
- 1. Chakraborty I, Maity P. COVID-19 outbreak: Migration, effects on society, global environment and prevention. Sci Total Environ. 2020;728:138882. doi:10.1016/j.scitotenv.2020.138882
- 2. Potì F, Pozzoli C, Adami M, Poli E, Costa LG. Treatments for COVID-19: Emerging drugs against the coronavirus. Acta Bio Medica Atenei Parmensis. 2020;91(2):118-136. doi:10.23750/abm.v91i2.9639
- 3. Taher M, Tik N, Susanti D. Drugs intervention study in COVID-19 management. Drug Metab Pers Ther. 2021;36(2):87-98. doi:10.1515/dmdi-2020-0173
- 4. Vohra M, Sharma AR, Satyamoorthy K, Rai PS. Pharmacogenomic considerations for repurposing of dexamethasone as a potential drug against SARS-CoV-2 infection. J Pers Med. 2021;18(4):389-398. doi:10.2217/pme-2020-0183
- 5. Ciobotaru OR, Lupu MN, Rebegea L, et al. Dexamethasone-chemical structure and mechanisms of action in prophylaxis of postoperative side effects. Rev Chim. 2019;70(3):843-847. doi:10.37358/RC.19.3.7017
- 6. Joshi S, Parkar J, Ansari A, et al. Role of favipiravir in the treatment of COVID-19. Int J Infect Dis. 2021;102:501-508. doi:10.1016/j.ijid.2020.10.069
- 7. Coomes EA, Haghbayan H. Favipiravir, an antiviral for COVID-19. J Antimicrob Chemother. 2020;75(7):2013-2014. doi:10.1093/jac/dkaa171
- 8. Lodangi N, Thawani V. Favipiravir in COVID-19. The Antiseptic. 2020;117:16-17.
- 9. Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;71(15):732-739. doi:10.1093/cid/ciaa237
- 10. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16(3):155-166. doi:10.1038/s41584-020-0372-x
- 11. Nakayama T, Sugano Y, Yokokawa T, et al. Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy. Eur J Heart Fail. 2017;19(4):490-498. doi:10.1002/ejhf.767
- 12. Iqbal BM, Buch A. Hormone receptor (ER, PR, HER2/neu) status and proliferation index marker (Ki-67) in breast cancers: Their onco-pathological correlation, shortcomings and future trends. Med J DY Patil Univ. 2016;9:674-679. doi:10.4103/0975-2870.194180
- 13. Akdemir A, Angeli A, Göktaş F, Eraslan Elma P, Karalı N, Supuran CT. Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme. J. Enzyme Inhib Med Chem. 2019;34(1):528-531. doi:10.1080/14756366.2018.1564045
- 14. Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 2012;4:17. doi:10.1186/1758-2946-4-17
- 15. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461. doi:10.1002/jcc.21334
- 16. Gavriatopoulou M, Ntanasis-Stathopoulos I, Korompoki E, et al. Emerging treatment strategies for COVID-19 infection. Clin Exp Med. 2021;21(2):167-179. doi:10.1007/s10238-020-00671-y
- 17. Sabe VT, Ntombela T, Jhamba LA, et al. Current trends in computer aided drug design and a highlight of drugs discovered via computational techniques: A review. Eur J Med Chem. 2021;224:113705. doi:10.1016/j.ejmech.2021.113705
- 18. Akinlalu AO, Chamundi A, Yakumbur DT, et al. Repurposing FDA-approved drugs against multiple proteins of SARS-CoV-2: An in silico study. Sci Afr. 2021;13:e00845. doi:10.1016/j.sciaf.2021.e00845
- 19. Tiwari G, Chauhan MS, Sharma D. Systematic in silico studies of corticosteroids and its binding affinities with glucocorticoid receptor for Covid-19 treatment: Ab-initio, molecular docking and MD simulation studies. Polycycl Aromat Compd. 2022. doi:10.1080/10406638.2022.2092878
- 20. Celı̇k I, Onay-Besı̇kcı̇ A, Ayhan-Kilcigı̇l G. Approach to the mechanism of action of hydroxychloroquine on SARS-CoV-2: a molecular docking study. J Biomol Struct Dyn. 2021;39(15):5792-5798. doi:10.1080/07391102.2020.1792993
- 21. Khelfaoui H, Harkati D, Saleh BA. Molecular docking, molecular dynamics simulations and reactivity, studies on approved drugs library targeting ACE2 and SARS-CoV-2 binding with ACE2. J Biomol Struct Dyn. 2021;39(18):7246-7262. doi:10.1080/07391102.2020.1803967
- 22. Wang Y, Li P, Rajpoot S, et al. Comparative assessment of favipiravir and remdesivir against human coronavirus NL63 in molecular docking and cell culture models. Sci Rep. 2021;11:23465. doi:10.1038/s41598-021-02972-y
- 23. Shi TT, Yu XX, Yan LJ, Xiao HT. Research progress of hydroxychloroquine and autophagy inhibitors on cancer. Cancer Chemother Pharmacol. 2017;79(2):287-294. doi:10.1007/s00280-016-3197-1
- 24. Murata H, Khattar NH, Gu L, Li GM. Roles of mismatch repair proteins hMSH2 and hMLH1 in the development of sporadic breast cancer. Cancer Lett. 2005;223(1):143-150. doi:10.1016/j.canlet.2004.09.039
- 25. Banin Hirata BK, Oda JM, Losi Guembarovski R, Ariza CB, de Oliveira CE, Watanabe MA. Molecular markers for breast cancer: prediction on tumor behavior. Dis Markers. 2014;2014:513158. doi:10.1155/2014/513158
- 26. Annett S, Fox OW, Vareslija D, Robson T. Dexamethasone promotes breast cancer stem cells in obese and not lean mice. Pharmacol Res Perspect. 2022;10(2):e00923. doi:10.1002/prp2.923
- 27. Cook KL, Wärri A, Soto-Pantoja DR, et al. Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clin Cancer Res. 2014;20(12):3222-3232. doi:10.1158/1078-0432.CCR-13-3227
- 28. Küçükcankurt F, Altıok N. HER2 reseptörüne karşı geliştirilen DNA aptamerlerin meme kanserinde tanı ve tedavi amaçlı kullanılması. IAU TFK J. 2020;3(1):35-39. doi:10.17932/IAU.TFK.2018.008/2020.301/tfk_v03i1005
COVID-19 Tedavisinde Kullanılan Bazı İlaçların Reseptör İlişkilerinin Modelleme Çalışmaları ile Değerlendirilmesi
Abstract
Amaç: COVID-19 tedavi sürecinde kullanılan ilaçların hücresel mekanizmalarla etkileşimlerinin araştırılması önemlidir. Bu çalışmada, COVID-19 tedavisinde kullanılan Deksametazon, Favipiravir ve Hidroksiklorokin adlı ilaçların östrojen reseptörü (ER), progesteron reseptörü (PR) ve insan epidermal büyüme faktörü reseptörü-2 (HER2) ile etkileşimlerinin belirlenmesi hedeflenmiştir.
Materyal ve Metot: Çalışma kapsamında, reseptörler ve ilaç moleküllerinin ilk olarak 3-boyutlu yapıları oluşturulmuş, ardından reseptör ve ilaç moleküllerinin her birinin bağlanma bölgesindeki etkileşimleri bilgisayar destekli ilaç tasarım yöntemi olan moleküler kenetlenme çalışmaları ile incelenmiş ve bağlanma afiniteleri değerlendirilmiştir.
Bulgular: Yapılan analizler sonucunda, Hidroksiklorokin adlı ilacın her üç reseptöre de en yüksek bağlanma afinitesi gösteren ilaç olduğu ve Deksametazon adlı ilacın ise reseptörlere en düşük afinite ile bağlandığı belirlenmiştir. Ayrıca, Deksametazonun ER ve HER2 reseptör aktif bölge aminoasitleri ile uygun olmayan interaksiyonlar geliştirdiği tespit edilmiştir.
Sonuç: Bu çalışmada, normal bireyler ve meme kanseri hastalarının Deksametazon, Favipiravir ve Hidroksiklorokin adlı ilaçları kullanması durumunda reseptör etkileşimlerinin nasıl olabileceğine ilişkin ön veriler sunulmuştur.
References
- 1. Chakraborty I, Maity P. COVID-19 outbreak: Migration, effects on society, global environment and prevention. Sci Total Environ. 2020;728:138882. doi:10.1016/j.scitotenv.2020.138882
- 2. Potì F, Pozzoli C, Adami M, Poli E, Costa LG. Treatments for COVID-19: Emerging drugs against the coronavirus. Acta Bio Medica Atenei Parmensis. 2020;91(2):118-136. doi:10.23750/abm.v91i2.9639
- 3. Taher M, Tik N, Susanti D. Drugs intervention study in COVID-19 management. Drug Metab Pers Ther. 2021;36(2):87-98. doi:10.1515/dmdi-2020-0173
- 4. Vohra M, Sharma AR, Satyamoorthy K, Rai PS. Pharmacogenomic considerations for repurposing of dexamethasone as a potential drug against SARS-CoV-2 infection. J Pers Med. 2021;18(4):389-398. doi:10.2217/pme-2020-0183
- 5. Ciobotaru OR, Lupu MN, Rebegea L, et al. Dexamethasone-chemical structure and mechanisms of action in prophylaxis of postoperative side effects. Rev Chim. 2019;70(3):843-847. doi:10.37358/RC.19.3.7017
- 6. Joshi S, Parkar J, Ansari A, et al. Role of favipiravir in the treatment of COVID-19. Int J Infect Dis. 2021;102:501-508. doi:10.1016/j.ijid.2020.10.069
- 7. Coomes EA, Haghbayan H. Favipiravir, an antiviral for COVID-19. J Antimicrob Chemother. 2020;75(7):2013-2014. doi:10.1093/jac/dkaa171
- 8. Lodangi N, Thawani V. Favipiravir in COVID-19. The Antiseptic. 2020;117:16-17.
- 9. Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;71(15):732-739. doi:10.1093/cid/ciaa237
- 10. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16(3):155-166. doi:10.1038/s41584-020-0372-x
- 11. Nakayama T, Sugano Y, Yokokawa T, et al. Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy. Eur J Heart Fail. 2017;19(4):490-498. doi:10.1002/ejhf.767
- 12. Iqbal BM, Buch A. Hormone receptor (ER, PR, HER2/neu) status and proliferation index marker (Ki-67) in breast cancers: Their onco-pathological correlation, shortcomings and future trends. Med J DY Patil Univ. 2016;9:674-679. doi:10.4103/0975-2870.194180
- 13. Akdemir A, Angeli A, Göktaş F, Eraslan Elma P, Karalı N, Supuran CT. Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme. J. Enzyme Inhib Med Chem. 2019;34(1):528-531. doi:10.1080/14756366.2018.1564045
- 14. Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 2012;4:17. doi:10.1186/1758-2946-4-17
- 15. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461. doi:10.1002/jcc.21334
- 16. Gavriatopoulou M, Ntanasis-Stathopoulos I, Korompoki E, et al. Emerging treatment strategies for COVID-19 infection. Clin Exp Med. 2021;21(2):167-179. doi:10.1007/s10238-020-00671-y
- 17. Sabe VT, Ntombela T, Jhamba LA, et al. Current trends in computer aided drug design and a highlight of drugs discovered via computational techniques: A review. Eur J Med Chem. 2021;224:113705. doi:10.1016/j.ejmech.2021.113705
- 18. Akinlalu AO, Chamundi A, Yakumbur DT, et al. Repurposing FDA-approved drugs against multiple proteins of SARS-CoV-2: An in silico study. Sci Afr. 2021;13:e00845. doi:10.1016/j.sciaf.2021.e00845
- 19. Tiwari G, Chauhan MS, Sharma D. Systematic in silico studies of corticosteroids and its binding affinities with glucocorticoid receptor for Covid-19 treatment: Ab-initio, molecular docking and MD simulation studies. Polycycl Aromat Compd. 2022. doi:10.1080/10406638.2022.2092878
- 20. Celı̇k I, Onay-Besı̇kcı̇ A, Ayhan-Kilcigı̇l G. Approach to the mechanism of action of hydroxychloroquine on SARS-CoV-2: a molecular docking study. J Biomol Struct Dyn. 2021;39(15):5792-5798. doi:10.1080/07391102.2020.1792993
- 21. Khelfaoui H, Harkati D, Saleh BA. Molecular docking, molecular dynamics simulations and reactivity, studies on approved drugs library targeting ACE2 and SARS-CoV-2 binding with ACE2. J Biomol Struct Dyn. 2021;39(18):7246-7262. doi:10.1080/07391102.2020.1803967
- 22. Wang Y, Li P, Rajpoot S, et al. Comparative assessment of favipiravir and remdesivir against human coronavirus NL63 in molecular docking and cell culture models. Sci Rep. 2021;11:23465. doi:10.1038/s41598-021-02972-y
- 23. Shi TT, Yu XX, Yan LJ, Xiao HT. Research progress of hydroxychloroquine and autophagy inhibitors on cancer. Cancer Chemother Pharmacol. 2017;79(2):287-294. doi:10.1007/s00280-016-3197-1
- 24. Murata H, Khattar NH, Gu L, Li GM. Roles of mismatch repair proteins hMSH2 and hMLH1 in the development of sporadic breast cancer. Cancer Lett. 2005;223(1):143-150. doi:10.1016/j.canlet.2004.09.039
- 25. Banin Hirata BK, Oda JM, Losi Guembarovski R, Ariza CB, de Oliveira CE, Watanabe MA. Molecular markers for breast cancer: prediction on tumor behavior. Dis Markers. 2014;2014:513158. doi:10.1155/2014/513158
- 26. Annett S, Fox OW, Vareslija D, Robson T. Dexamethasone promotes breast cancer stem cells in obese and not lean mice. Pharmacol Res Perspect. 2022;10(2):e00923. doi:10.1002/prp2.923
- 27. Cook KL, Wärri A, Soto-Pantoja DR, et al. Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clin Cancer Res. 2014;20(12):3222-3232. doi:10.1158/1078-0432.CCR-13-3227
- 28. Küçükcankurt F, Altıok N. HER2 reseptörüne karşı geliştirilen DNA aptamerlerin meme kanserinde tanı ve tedavi amaçlı kullanılması. IAU TFK J. 2020;3(1):35-39. doi:10.17932/IAU.TFK.2018.008/2020.301/tfk_v03i1005
There are 28 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Research article |
| Authors | |
| Early Pub Date | March 2, 2023 |
| Publication Date | March 5, 2023 |
| Submission Date | August 5, 2022 |
| Acceptance Date | January 15, 2023 |
| Published in Issue | Year 2023 Volume: 8 Issue: 1 |
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