Molecular docking analysis on 16 therapeutic ligands of Ocimum tenuiflorum L. (Tulasi) and their prospects in drug design for COVID-19

Authors

  • Guruprasad Anantharam Department of Plant Biology and Plant Biotechnology, Presidency College (Autonomous), Chennai – 600 005, Tamil Nadu, India
  • S. Geetha Department of Plant Biology and Plant Biotechnology, Presidency College (Autonomous), Chennai – 600 005, Tamil Nadu, India
  • P. Santhana Pandi Department of Plant Biology and Plant Biotechnology, Presidency College (Autonomous), Chennai – 600 005, Tamil Nadu, India
  • N. Krithika Department of Plant Biology and Plant Biotechnology, Presidency College (Autonomous), Chennai – 600 005, Tamil Nadu, India
  • C. V. Chittibabu Department of Plant Biology and Plant Biotechnology, Presidency College (Autonomous), Chennai – 600 005, Tamil Nadu, India

DOI:

https://doi.org/10.25081/jp.2022.v14.7842

Keywords:

COVID-19, Molecular docking, PyRx software, Rosmarinic acid, 6LU7 protease, 6Y2E protease

Abstract

The PyRx software and Discovery studio were used in the present molecular docking studies of the 16 ligands of Ocimum tenuiflorum L., selected based on their high therapeutic potentials, viz., (E)-6-hydroxy-4,6-dimethylhept-3-en-2-one, Apigenin, Bieugenol, Cirsilineol, Cirsimaritin, β-Caryophyllene epoxide, Dehydrodieugenol B, Eugenol, Ferulaldehyde, Isothymonin, Isothymusin, Linalool, Luteolin, Ocimarin, Rosmarinic acid, and Thymol. Saquinavir was used as a positive control. The binding affinities of the 16 ligands to the main proteases of COVID-19 6LU7 and 6Y2E (critical for viral replication) and their ability to arrest the virus replication were recorded. The binding affinities of the ligands to 6LU7 and 6Y2E ranged from -4.3 and -4.7 kcal/mol (for (E)-6-hydroxy-4,6-dimethylhept-3-en-2-one) to -7.6 (for Rosmarinic acid to both target proteins). While the corresponding values for the control drug Saquinavir were -7.8 and -7.6 respectively. The Rosmarinic acid, in binding with both the proteases (-7.6 and -7.6 kcal/mol) showed six conventional hydrogen bonds, one carbon hydrogen bond (ASP 153 had one conventional hydrogen bond and one carbon hydrogen bond), one Pi-alkyl bond, one Pi-Pi stacked bond, eight van der waals bonds for 6LU7 protease; it formed three conventional hydrogen bonds, two Pi-alkyl bonds, one unfavourable donor – donor bond and 14 van der waals bonds with 6Y2E protease. The control drug – Saquinavir in binding with 6LU7 protease showed 12 van der waals, one alkyl, one Pi-alkyl, one Pi-cation, one Pi-stacked and four conventional hydrogen bonds, which indicates that it has less affinity when compared with Rosmarinic acid. Similarly, the control drug on binding with 6Y2E protease exhibited ten van der waals, four Pi-alkyl, one cation and three hydrogen bonds. The results are in conformity to similar other studies, and herald a promising scope for Rosmarinic acid as lead molecule in the drug discovery for COVID-19.

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References

Bhadran, S., George, S. A., Malla, S., & Puttaraju, H. B. (2021). In silico prediction and molecular docking study on the interaction of bioactive compounds of Adenanthera pavonina exploring the potential antifungal activity against Candida glabrata cell wall proteins. International Journal of Pharmaceutical Sciences and Drug Research, 13(1), 51–59.

Chaudari, R. N., Khan, S. L., Chaudhary, R. S., Jain, S. P., & Sidduqui, F. A. (2020). Β-sitosterol: isolation from Muntingia calabura Linn bark extract, structural elucidation and molecular docking studies as potential inhibitor of sars-cov-2 mpro (COVID-19). Asian Journal of Pharmaceutical and Clinical Research, 13(5), 204–209. https://doi.org/10.22159/ajpcr.2020.v13i5.37909

Chen, S. J. (2014). A potential target of tanshinone IIA for acute promyelocytic leukemia revealed by inverse docking and drug repurposing. Asian Pacific Journal of Cancer Prevention, 15(10), 4301–4305. https://doi.org/10.7314/apjcp.2014.15.10.4301

Chojnacka, K., Witek-Krowiak, A., Skrzypczak, D., Mikula, K., & Młynarz, P. (2020). Phytochemicals containing biologically active polyphenols as an effective agent against Covid-19-inducing coronavirus. Journal of Functional Foods, 73, 104146. https://doi.org/10.1016/j.jff.2020.104146

Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717. https://doi.org/10.1038/srep42717

Dallakyan, S., & Olson, A. J. (2015). Small-molecule library screening by docking with PyRx. In J. E. Hempel, C. H. Williams & C. C. Hong (Eds.), Methods in Molecular Biology: Vol. 1263. Chemical Biology: Methods and Protocols. New York: Humana Press. https://doi.org/10.1007/978-1-4939-2269-7_19

Herowati, R., & Widodo, G. P. (2014). Molecular docking studies of chemical constituents of Tinospora cordifolia on glycogen phosphorylase. Procedia Chemistry, 13, 63–68. https://doi.org/10.1016/j.proche.2014.12.007

Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., & Bolton, E. E. (2019). PubChem 2019 update: Improved access to chemical data. Nucleic Acids Research, 47(D1), D1102–D1109. https://doi.org/10.1093/nar/gky1033

Kiran, G., Karthik, L., Shree Devi, M. S., Sathiyarajeswaran, P., Kanakavalli, K., Kumar, K. M., & Ramesh Kumar, D. (2020). In Silico computational screening of Kabasura Kudineer - Official Siddha Formulation and JACOM against SARS-CoV-2 spike protein. Journal of Ayurveda and Integrative Medicine, 13(1), 100324. https://doi.org/10.1016/j.jaim.2020.05.009

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, 4-17. https://doi.org/10.1016/j.addr.2012.09.019

Ounthaisong, U., & Tangyuenyongwatana, P. (2017). Cross-docking study of flavonoids against tyrosinase enzymes using PyRx 0.8 virtual screening tool. Thai Journal of Pharmaceutical Sciences, 41, 189–192.

Pandey, G., & Sharma, M. (2010). Pharmacological activities of Ocimum sanctum (Tulsi): A review. International Journal of Pharmaceutical Sciences Review and Research, 5(1), 61–66.

Peele, K. A., Durthi, C. P., Srihansa, T., Krupanidhi, S., Ayyagari, V. S., Babu, D. J., Indira, M., Reddy, A. R., & Venkateswarulu, T. C. (2020). Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2: A computational study. Informatics in Medicine Unlocked, 19, 100345. https://doi.org/10.1016/j.imu.2020.100345

Raj, R. (2021). Analysis of non-structural proteins, NSPs of SARS-CoV-2 as targets for computational drug designing. Biochemistry and Biophysics Reports, 25, 100847. https://doi.org/10.1016/j.bbrep.2020.100847

Ramírez, D., & Caballero, J. (2018). Is it reliable to take the molecular docking top scoring position as the best solution without considering available structural data? Molecules, 23(5), 1038. https://doi.org/10.3390/molecules23051038

Sampangi-Ramaiah, M. H., Vishwakarma, R., & Shaanker, R. U. (2020). Molecular docking analysis of selected natural products from plants for inhibition of SARS-CoV-2 main protease. Current Science, 118(7), 1087–1092. https://doi.org/10.18520/cs/v118/i7/1087-1092

Shaker, B., Yu, M. S., Lee, J., Lee, Y., Jung, C., & Na, D. (2020). User guide for the discovery of potential drugs via protein structure prediction and ligand docking simulation. Journal of Microbiology, 58(3), 235–244. https://doi.org/10.1007/s12275-020-9563-z

Singh, D., & Chaudhuri, P. K. (2018). A review on phytochemical and pharmacological properties of Holy basil (Ocimum sanctum L.). Industrial Crops and Products, 118, 367–382. https://doi.org/10.1016/j.indcrop.2018.03.048

Sisakht, M., Mahmoodzadeh, A., & Darabian, M. (2021). Plant-derived chemicals as potential inhibitors of SARS-CoV-2 main protease (6LU7), a virtual screening study. Phytotherapy Research, 35(6), 3262–3274. https://doi.org/10.1002/ptr.7041

Siva, M., Shanmugam, K., Shanmugam, B., Venkata Subbaiah, G., Ravi., S., Sathyavelu., K., & Mallikarjuna., K. (2016). Ocimum sanctum: a review on the pharmacological properties. Int. J. Basic Clin. Pharmacol, 5, 558–565. https://doi.org/10.18203/2319-2003.ijbcp20161491

Soni, A., & Sosa, S. E. (2013). Phytochemical analysis and free radical scavenging potential of herbal and medicinal plant extracts. Journal of Pharmacognosy Phytochemistry, 2, 22–29.

Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455-461. https://doi.org/10.1002/jcc21334

Wu, C., Liu, Y., Yang, Y., Zhang, P., Zhong, W., Wang, Y., Wang, Q., Xu, Y., Li, M., Li, X., Zheng, M., Chen, L., & Li, H. (2020). Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica. B, 10(5), 766–788. https://doi.org/10.1016/j.apsb.2020.02.008

Yuliana, D., Bahtiar, F. I., & Najib, A. (2013). In Silico screening of chemical compounds from roselle (Hibiscus Sabdariffa) as angiotensin-i converting enzyme inhibitor used PyRx Program. ARPN Journal of Science and Technology, 3(12), 1158–1160.

Published

27-07-2022

How to Cite

Anantharam, G., Geetha, S., Santhana Pandi, P., Krithika, N., & Chittibabu, C. V. (2022). Molecular docking analysis on 16 therapeutic ligands of Ocimum tenuiflorum L. (Tulasi) and their prospects in drug design for COVID-19. Journal of Phytology, 14, 76–85. https://doi.org/10.25081/jp.2022.v14.7842

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