Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking
Journal of Pharmaceutical Research International,
Page 186-191
DOI:
10.9734/jpri/2021/v33i29B31603
Abstract
In this study, vitamin D has shown greater efficacy of binding with Mpro of COVID-19 compared to the recently recommended drugs. The docking study was simulated to streamline interaction effects of Vitamin D, Remdesivir, Chloroquine, Hydroxychloroquine, Aspirin, and Azithromycin complexes with the active site of Mpro. Vitamin D is found to have the highest potential interaction in terms of total H-bond, van der Waal, torsional, and desolvation energy which were the lowest among all the selected drugs. The hydroxyl group of vitamin D and the thiol group of Mpro cysteine had played a leading role in increasing Vitamin D binding and stability with the Mpro pocket by contribution to the inception of three hydrogen bonds. The study recommend that vitamin D can be added to the COVID-19 treatment protocol, which may have the desired effect on viral replication inhibition and decreases mortality.
Keywords:
- Molecular docking
- vitamin D
- Mpro
- COVID-19
- thiol group
How to Cite
Al-Mazaideh, G. M., Shalayel, M. H., Al-Swailmi, F. K., & Aladaileh, S. H. (2021). Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking. Journal of Pharmaceutical Research International, 33(29B), 186-191. https://doi.org/10.9734/jpri/2021/v33i29B31603
References
1. Roosa K, Lee Y, Kirpich A, Rothenberg R, Hyman JM, Yan P, Chowell G. Real-time forecasts of the COVID-19 epidemic in China from February 5th to February 24th, 2020. Infect. Disease Mod. 2020;5:256-263.
2. Joshi T, Joshi T, Sharma P, Mathpal S, Pundir H, Bhatt V, Chandra S. In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. Eur. Rev. Med. Pharmacol. Sci. 2020;24(8):4529-4536.
3. Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, Becker S, Rox K, Hilgenfeld R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368:409-412.
4. Narkhede RR, Pise AV, Cheke RS, Cheke RS, Shinde SD. Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences. Nat. Prod. Bioprospect. 2020;10:297-306.
Available:https://doi.org/10.1007/s13659-020-00253-1..
5. Baez-Santos YM, St John SE and Mesecar AD. The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds. Antivir. Res. 2015;115:21-38.
6. Motiwale M , Yadav NS, Kumar S, Kushwaha T, Choudhir G, Sharma S, Singour KP. Finding potent inhibitors for COVID-19 main protease (Mpro): an in silico approach using SARS-CoV-3CL protease inhibitors for combating CORONA. J. Biomol. Struct. Dyn. 2020;8:1-12.
DOI: 10.1080/07391102.2020.1829501.
7. Jung SM, Akhmetzhanov AR, Hayashi K, Linton NM, Yang Y, Yuan B, Kobayashi T, Kinoshita R and Nishiura H. Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases. J. Clin. Med. 2020;9(2):523.
8. Brooijmans N, Kuntz ID. Molecular recognition and docking algorithms. Annual Rev. Biophys. Biomol. Struct. 2003;32(1):335-373.
9. Lybrand TP. Ligand—protein docking and rational drug design. Curr. Opin. Struct. Biol. 1995. 5(2):224-228.
10. Martineau AR, Jolliffe DA, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Janssens W, Jensen ME, Kerley CP, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S, Stelmach I, Trilok Kumar G, Urashima M, Camargo CA, Griffiths CJ and Hooper RL. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol. Assess. 2019;23(2):1-44.
DOI: 10.3310/hta23020.
PMID: 30675873;
PMCID: PMC6369419.
11. Shalayel MHF, Al-Qahtani AM, Huneif MA. Vitamin D or flu vaccine-benefits over adverse effects. Br. Biomed Bull. 2018;6:311.
12. Hansdottir S, Monick MM. Vitamin D effects on lung immunity and respiratory diseases. Vitam. Horm. 2011;86:217- 37.
13. Xu Y, Baylink DJ, Chen CS, Reeves ME, Xiao J, Lacy C, Lau E, Cao H. The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J. Transl. Med. 2020;18: 322.
Available:https://doi.org/10.1186/s12967-020-02488-5.
14. Shalayel MH, Al-Mazaideh GM, Aladaileh SH, Al-Swailm FK and Al-Thiaba MG. Vitamin D is a potential inhibitor of COVID-19: In silico molecular docking to the binding site of SARS-CoV-2 endoribonuclease Nsp15. Pak. J. Pharm. Sci. 2020;33(5):2179-2186.
DOI: org/10.36721/PJPS.2020.33.5.REG.2179-2186.1.
15. Jin Z, Du X, Yechun Xu, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;1-5.
16. Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ. Computational protein-ligand docking and virtual drug screening with the Auto Dock suite. Nat. Protoc. 2016;11(5):905-19.
DOI: 10.1038/nprot.2016.051.
17. Rizvi SMD, Shakil S, Haneef M. A simple click by click protocol to perform docking: Auto Dock 4.2 made easy for non-bioinformaticians. EXCLI J. 2013;12:831.
18. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271.
19. Zhang J, Shen X, Yan Y, Wang Y, Cheng Y. Discovery of anti-SARS-CoV-2 agents from commercially available flavor via docking screening. OSF Preprints; 2020.
Available:https://doi.org/10.31219/osf.io/vjch2
20. Pell B, Kuang Y, Viboud C and Chowell G. Using phenomenological models for forecasting the 2015 Ebola challenge. Epidemics. 2018;22:62-70.
Available:http://doi.org/10.1016/j.epidem.2016.11.002
21. Chauhan A, Kalra S. Identification of potent COVID-19 main protease (MPRO) inhibitors from flavonoids. Res. square. Preprint; 2020.
DOI: https://doi.org/10.21203/rs.3.rs-34497/v1.
22. Yang H, Xie W, Xue X, Yang K, Ma J, Liang W, Zhao Q, Zhou Z, Pei D, Ziebuhr J, Hilgenfeld R, Yuen KY, Wong L, Gao G, Chen S, Chen Z, Ma D, Bartlam M, Rao Z. Design of wide-spectrum inhibitors targeting coronavirus main proteases. PLoS Biol. 2005;3(10):e324.
23. Larriba MJ, García de Herreros A and Muñoz A. Vitamin D and the Epithelial to Mesenchymal Transition. Stem Cells Inter; 2016.
Article ID: 6213872.
Available:https://doi.org/10.1155/2016/6213872.
24. Bikle DD. Vitamin D metabolism, mechanism of action and clinical applications. Chem. Biol. 2014;21(3):319-329.
DOI: 10.1016/j.chembiol.2013.12.016.
2. Joshi T, Joshi T, Sharma P, Mathpal S, Pundir H, Bhatt V, Chandra S. In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. Eur. Rev. Med. Pharmacol. Sci. 2020;24(8):4529-4536.
3. Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, Becker S, Rox K, Hilgenfeld R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368:409-412.
4. Narkhede RR, Pise AV, Cheke RS, Cheke RS, Shinde SD. Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences. Nat. Prod. Bioprospect. 2020;10:297-306.
Available:https://doi.org/10.1007/s13659-020-00253-1..
5. Baez-Santos YM, St John SE and Mesecar AD. The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds. Antivir. Res. 2015;115:21-38.
6. Motiwale M , Yadav NS, Kumar S, Kushwaha T, Choudhir G, Sharma S, Singour KP. Finding potent inhibitors for COVID-19 main protease (Mpro): an in silico approach using SARS-CoV-3CL protease inhibitors for combating CORONA. J. Biomol. Struct. Dyn. 2020;8:1-12.
DOI: 10.1080/07391102.2020.1829501.
7. Jung SM, Akhmetzhanov AR, Hayashi K, Linton NM, Yang Y, Yuan B, Kobayashi T, Kinoshita R and Nishiura H. Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases. J. Clin. Med. 2020;9(2):523.
8. Brooijmans N, Kuntz ID. Molecular recognition and docking algorithms. Annual Rev. Biophys. Biomol. Struct. 2003;32(1):335-373.
9. Lybrand TP. Ligand—protein docking and rational drug design. Curr. Opin. Struct. Biol. 1995. 5(2):224-228.
10. Martineau AR, Jolliffe DA, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Janssens W, Jensen ME, Kerley CP, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S, Stelmach I, Trilok Kumar G, Urashima M, Camargo CA, Griffiths CJ and Hooper RL. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol. Assess. 2019;23(2):1-44.
DOI: 10.3310/hta23020.
PMID: 30675873;
PMCID: PMC6369419.
11. Shalayel MHF, Al-Qahtani AM, Huneif MA. Vitamin D or flu vaccine-benefits over adverse effects. Br. Biomed Bull. 2018;6:311.
12. Hansdottir S, Monick MM. Vitamin D effects on lung immunity and respiratory diseases. Vitam. Horm. 2011;86:217- 37.
13. Xu Y, Baylink DJ, Chen CS, Reeves ME, Xiao J, Lacy C, Lau E, Cao H. The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J. Transl. Med. 2020;18: 322.
Available:https://doi.org/10.1186/s12967-020-02488-5.
14. Shalayel MH, Al-Mazaideh GM, Aladaileh SH, Al-Swailm FK and Al-Thiaba MG. Vitamin D is a potential inhibitor of COVID-19: In silico molecular docking to the binding site of SARS-CoV-2 endoribonuclease Nsp15. Pak. J. Pharm. Sci. 2020;33(5):2179-2186.
DOI: org/10.36721/PJPS.2020.33.5.REG.2179-2186.1.
15. Jin Z, Du X, Yechun Xu, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;1-5.
16. Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ. Computational protein-ligand docking and virtual drug screening with the Auto Dock suite. Nat. Protoc. 2016;11(5):905-19.
DOI: 10.1038/nprot.2016.051.
17. Rizvi SMD, Shakil S, Haneef M. A simple click by click protocol to perform docking: Auto Dock 4.2 made easy for non-bioinformaticians. EXCLI J. 2013;12:831.
18. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271.
19. Zhang J, Shen X, Yan Y, Wang Y, Cheng Y. Discovery of anti-SARS-CoV-2 agents from commercially available flavor via docking screening. OSF Preprints; 2020.
Available:https://doi.org/10.31219/osf.io/vjch2
20. Pell B, Kuang Y, Viboud C and Chowell G. Using phenomenological models for forecasting the 2015 Ebola challenge. Epidemics. 2018;22:62-70.
Available:http://doi.org/10.1016/j.epidem.2016.11.002
21. Chauhan A, Kalra S. Identification of potent COVID-19 main protease (MPRO) inhibitors from flavonoids. Res. square. Preprint; 2020.
DOI: https://doi.org/10.21203/rs.3.rs-34497/v1.
22. Yang H, Xie W, Xue X, Yang K, Ma J, Liang W, Zhao Q, Zhou Z, Pei D, Ziebuhr J, Hilgenfeld R, Yuen KY, Wong L, Gao G, Chen S, Chen Z, Ma D, Bartlam M, Rao Z. Design of wide-spectrum inhibitors targeting coronavirus main proteases. PLoS Biol. 2005;3(10):e324.
23. Larriba MJ, García de Herreros A and Muñoz A. Vitamin D and the Epithelial to Mesenchymal Transition. Stem Cells Inter; 2016.
Article ID: 6213872.
Available:https://doi.org/10.1155/2016/6213872.
24. Bikle DD. Vitamin D metabolism, mechanism of action and clinical applications. Chem. Biol. 2014;21(3):319-329.
DOI: 10.1016/j.chembiol.2013.12.016.
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