ABSTRACT:
The SARS-CoV-2 virus is the infectious disease known as coronavirus disease (COVID-19). The majority of COVID-19 patients will have mild to moderate symptoms and recover without additional care. However, some people will get serious illnesses and need medical attention. Designing novel medications and testing them for inhibitory action against the corona virus's primary targets could be a successful technique for the advancement of the drug discovery process and the treatment of corona virus disease in the context of the COVID-19 pandemic, which is spreading quickly. The objective of this work was to evaluate the physical-chemical, pharmacokinetic parameters (absorption, distribution, metabolism, excretion and toxicity) and pharmacodynamic parameters (bioactivity and adverse reactions) of Substituted thiadiazole by means of in-silico computational prediction. Online software such as Pre-ADMET, Molinspiration and Rule of Five were used for the analysis. In-silico results allow us to conclude that substituted thiadiazole is predicted to be a potential future drug candidate, due to its relevant Drug-likeness profile, bioavailability, excellent liposolubility and adequate pharmacokinetics, including at the level of CNS, penetrating the blood-brain barrier. Molecular docking studies of 20 designed compounds have also been performed to screen the inhibitory activity towards against protein target COVID-19 main protease (PDB: 6LU7). Among all the compounds C3 exhibited the most significant affinity score against COVID-19 main protease (PDB: 6LU7) and Shown best significant hydrogen bonds interaction at the active site of protein.
Cite this article:
Deshmukh Nitin, Soni Love Kumar. Prediction of In-silico ADMET Properties and Molecular docking study of Substituted Thiadiazole for screening of Antiviral activity against protein target Covid-19 main protease. Research Journal of Pharmacy and Technology. 2023; 16(12):5802-7. doi: 10.52711/0974-360X.2023.00939
Cite(Electronic):
Deshmukh Nitin, Soni Love Kumar. Prediction of In-silico ADMET Properties and Molecular docking study of Substituted Thiadiazole for screening of Antiviral activity against protein target Covid-19 main protease. Research Journal of Pharmacy and Technology. 2023; 16(12):5802-7. doi: 10.52711/0974-360X.2023.00939 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-12-40
6.0 REFERENCES:
1. Christine M. Psychological impact on people Due to Pandemic of Covid-19 in selected Areas of Mumbai, Asian J. Nursing Education and Research. 2021; 11(4): 541-551. doi.org/10.52711/2349-2996.2021.00128.
2. Kim J.M. Chung Y.S. Identification of Coronavirus Isolated from a Patient in Korea with COVID-19. Osong Public Health Res Perspect. 2020; 11: 3–7. doi.org/10.24171/j.phrp.2020.11.1.02
3. Choudhary M. Gopichandran L. Post Covid-19 Complications: A New Dimension of Awareness for Healthcare Workers, Asian Journal of Nursing Education and Research. 2021; 11(4): 455-458. doi.org/10.52711/2349-2996.2021.00110
4. Nihala N. Chathappady H. Sheeba P. Corona Viruses: A Review on SARS, MERS and COVID-19, Microbiology Insights. 2021; 14: 1–8. doi.org/10.1177/11786361211002481
5. Balai M. UK Variant COVID-19, Asian J. Nursing Education and Research. 2021; 11(4):601-4. doi: 10.52711/2349-2996.2021.00140
6. Ben H. Hua G. Peng Z. Zheng-Li S. Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews Microbiology. 2021; 19: 141–154. doi.org/10.1038/s41579-022-00711-2
7. Dawood A. Using Remdesivir and Dexamethasone for Treatment of SARS-CoV-2 Shortens the patient's stay in the Hospital, Asian Journal of Pharmaceutical Research. 2021; 11(2):138-140. doi.org/10.52711/2231-5691.2021.00026
8. Jain M. Shashikant. Barhate D. Favipiravir has been investigated for the treatment of life-threatening pathogens such as Ebola virus, Lassa virus, and now COVID-19: A Review. Asian J. Pharm. Res. 2021; 11(1): 39-42. doi.org/10.5958/2231-5691.2021.00008.3
9. Singh G. Pawan. Design of new bis-triazolyl structure for identification of inhibitory activity on COVID-19 main protease by molecular docking approach. Journal of Molecular Structure. 2022; 1-7. doi.org/10.1016/j.molstruc.2021.131858
10. Sindhu. T. Arathi. N. Synthesis, Molecular Docking and Antibacterial Studies of Novel Azole derivatives as Enoyl ACP Reductase Inhibitor in Escherichia coli. Asian J. Res. Pharm. Sci. 2019; 9(3): 174-180. doi.org/ 10.5958/2231-5659.2019.00027.4
11. Al-Mulla A. A Review: Biological Importance of Heterocyclic Compounds. Der Pharma Chemica. 2017; 9(13):141-147.
12. Geethapriya, Karthikeyan E. Mannich bases: an overview of heterocyclic compound with various biological activities; International journal of pharmaceutical sciences and research. 2021; 12(12): 6151-65. doi.org/10.13040/IJPSR.0975-8232.12(12).6151-65
13. Corona virus disease (COVID-2019) situation reports, (n.d.). www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/ (accessed August 9, 2020).
14. Haribabu J. Garisetti V. Design and synthesis of heterocyclic azole based bioactive compounds: Molecular structures, quantum simulation, and mechanistic studies through docking as multi-target inhibitors of SARS-CoV-2 and cytotoxicity. Journal of molecular structure. 2022; 2(1): 1-17. doi.org/10.1016/j.molstruc.2021.131782
15. Georgeta S. 2-Amino-1,3,4-thiadiazoles as prospective agents in trypanosomiasis and other parasitoses. Acta Pharm. 2020; 70: 259–290. doi.org/10.2478/acph-2020-0031
16. Mehta D. Taya P. Das R. Dua K. Design, Synthesis and Molecular Docking Studies of Novel Thiadiazole Analogues with Potential Antimicrobial and Antiinflammatory Activities, Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry. 2019; 18: 91-109. doi.org/10.2174/1871520619666190307162442
17. Katsila T. Spyroulias G. Patrinos G. Matsoukas M. Computational approaches in target identification and drug discovery. Comput. Struct. Biotechnol. J., 2016; 14: 177-184. doi.org/10.1016/j.csbj.2016.04.004
18. Kushwaha N. Kushwaha S. Biological Activities of Thiadiazole Derivatives: A Review. International Journal of Chemtech Research. 2015; 4(2) :517-531.
19. Yeni S. Fajar M. In silico toxicity prediction of 1-phenyl-1-(quinazolin-4-yl) ethanol compounds by using Toxtree, pkCSM and PreADMET. Pharmaciana. 2018; 8(2): 205-216. doi.org/10.12928/pharmaciana.v8i2.9508
20. Jagannathan R. Characterization of Drug-like Chemical Space for Cytotoxic Marine Metabolites Using Multivariate Method. ACS Omega. 2019; 4(3):5402-5411. doi.org/10.1021/acsomega.8b01764
21. Da Silva M. Synthesis, Antiproliferative Activity and Molecular Properties Predictions of Galloyl Derivative. Molecules. 2015; 20(4):5360-5373. doi.org/10.3390/molecules20045360
22. Chelamalla R. Makula A. Molecular docking studies and ADMET Predictions of Pyrimidine Coumarin Scaffolds as Potential IDO Inhibitors. Asian J. Research Chem. 2017; 10(3):331-340. doi.org/10.5958/0974-4150.2017.00056.6
23. Mani S. Swargiary G. Gulati S. Gupta S. Jindal D. Molecular docking and ADMET studies to predict the anti-breast cancer effect of aloin by targeting estrogen and progesterone receptors. Materials Today: Proceedings. 2023; 20(5):360-373. doi.org/10.1016/j.matpr.2021.06.362
24. Shafqat N. Muhammad S. Ahmad S. Syed A. Muhammad I. Hameed A. Synthesis, spectral characterization and in vitro antibacterial evaluation and Petra/Osiris/ Molinspiration analyses of new Palladium(II) iodide complexes with thioamides. Alexandria Journal of Medicine. 2016; 52(3): 279-288. doi.org/10.1016/j.ajme.2015.10.003
25. Sheikh J. Parvez A. Ingle V. Juneja H. Dongre R. Chohan Z. Synthesis, biopharmaceutical characterization, antimicrobial and antioxidant activities of 1-(40 -O-b-d-glucopyranosyloxy-20 - hydroxyphenyl)-3-aryl-propane-1,3-diones. Eur J Med Chem. 2011; 46:1390–9.
26. Parvez A. Meshram J. Tiwari V. Sheikh J. Dongre R. Youssoufi M. Pharmacophores modeling in terms of prediction of theoretical physico-chemical properties and verification by experimental correlations of novel coumarin derivatives produced via Betti’s protocol. Eur J Med Chem. 2010;45: 4370–8.
27. Uddin N. Sirajuddin M. Uddin N. Ullah H. Ali S. Tariq M. Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates. Spectrochim Acta A. 2015;140:563–74. doi.org/10.1016/j.saa.2014.12.062
28. Rajkumar T. Shirisha P. Shah F. Shaik A. Nagaiah T. Sulthana A. prediction of molecular properties, bioactivity and docking of novel hydrazines. international journal of trends in pharmacy and life sciences. 2016; 2(1): 757-768.
29. Husain A. Aftab A. Khan A. Mohd A. Bhutani R. Fahad A. Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents. Saudi Pharmaceutical Journal. 2015; 4(2): 3-11. doi.org/10.1016/j.jsps.2015.02.008
30. Patadiya N. Vaghela V. Design, in-silico ADME Study and molecular docking study of novel quinoline-4-on derivatives as Factor Xa Inhibitor as Potential anti-coagulating agents. Asian Journal of Pharmaceutical Research. 2022; 12(3):207-1. doi.org/10.52711/2231-5691.2022.00034
31. Siva Kumar R. Shaik N. Computer Aided Docking Studies on Antiviral Drugs for Bird Flu. Asian J. Research Chem. 2010; 3(2):370-373.
32. Devgan M. Homology modeling and molecular docking studies of DNA replication licensing factor minichromosome maintenance protein 5 (MCM5). Asian J. Pharm. Tech. 2015; 5(1):17-22. doi.org/10.5958/2231-5713.2015.00004.5
33. Sindhu. T. Arathi K. Antiviral screening of Clerodol derivatives as COV 2 main protease inhibitor in Novel Corona Virus Disease: In silico approaches. Asian J. Pharm. Tech. 2020; 10(2):60-64. doi.org/10.5958/2231-5713.2020.00012.4