Inhibitory Potential of Phytochemicals on Interleukin-6-Mediated T-Cell Reduction in COVID-19 Patients: A Computational Approach
Autor: | Anam Naz, Faryal Mehwish Awan, Ayesha Zahid, Mubashir Hassan, Arif Malik, Bisma Rauff, Sajjad Ahmad, Tassadaq Hussain Jafar, Aqsa Ikram, Mansoor Hafeez |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Coronavirus disease 2019 (COVID-19)
QH301-705.5 T cell Disease Pharmacology Biochemistry Reduction (complexity) 03 medical and health sciences medicine drug designing Biology (General) Interleukin 6 Molecular Biology 030304 developmental biology Original Research 0303 health sciences Inhibitory potential phytocompounds biology 030306 microbiology business.industry Applied Mathematics interleukin-6 COVID-19 molecular docking Computer Science Applications Computational Mathematics medicine.anatomical_structure Death toll biology.protein business |
Zdroj: | Bioinformatics and Biology Insights Bioinformatics and Biology Insights, Vol 15 (2021) |
ISSN: | 1177-9322 |
Popis: | Background: A recent COVID-19 pandemic has resulted in a large death toll rate globally and even no cure or vaccine has been successfully employed to combat this disease. Patients have been reported with multi-organ dysfunction along with acute respiratory distress syndrome which implies a critical situation for patients and made them difficult to breathe and survive. Moreover, pathology of COVID-19 is also related to cytokine storm which indicates the elevated levels of interleukin (IL)-1, IL-6, IL-12, and IL-18 along with tumor necrosis factor (TNF)-α. Among them, the proinflammatory cytokine IL-6 has been reported to be induced via binding of severe acute respiratory syndrome coronavirus 2 (SARS)-CoV-2 to the host receptors. Methodology: Interleukin-6 blockade has been proposed to constitute novel therapeutics against COVID-19. Thus, in this study, 15 phytocompounds with known antiviral activity have been subjected to test for their inhibitory effect on IL-6. Based on the affinity prediction, top 3 compounds (isoorientin, lupeol, and andrographolide) with best scores were selected for 50 ns molecular dynamics simulation and MMGB/PBSA binding free energy analysis. Results: Three phytocompounds including isoorientin, lupeol, and andrographolide have shown strong interactions with the targeted protein IL-6 with least binding energies (−7.1 to −7.7 kcal/mol). Drug-likeness and ADMET profiles of prioritized phytocompounds are also very prominsing and can be further tested to be potential IL-6 blockers and thus benficial for COVID-19 treatment. The moelcular dynamics simulation couple with MMGB/PBSA binding free energy estimation validated conformational stability of the ligands and stronger intermolecular binding. The mean RMSD of the complexes is as: IL6-isoorientin complex (3.97 Å ± 0.77), IL6-lupeol (3.97 Å ± 0.76), and IL6-andrographolide complex (3.96 Å ± 0.77). In addition, the stability observation was affirmed by compounds mean RMSD: isoorientin (0.72 Å ± 0.32), lupeol (mean 0.38 Å ± 0.08), and andrographolide (1.09 Å ± 0.49). A similar strong agreement on systems stability was unraveled by MMGB/PBSA that found net binding net ~ −20 kcal/mol for the complexes dominated by van der Waal interaction energy. Conclusion: It has been predicted that proposing potential IL-6 inhibitors with less side effects can help critical COVID-19 patients because it may control the cytokine storm, a major responsible factor of its pathogenesis. In this study, 3 potential phytocompounds have been proposed to have inhibitory effect on IL-6 that can be tested as potential therapeutic options against SARS-CoV-2. |
Databáze: | OpenAIRE |
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