In-silico Identification of the Novel Anti EGFR Compounds from Ginger Through Virtual Screening and Molecular Docking Analysis

Introduction: The EGFR receptor tyrosine kinase is revealed to be the critical biomarker involved in cancer metastasis and proliferation. The FDA approved drugs have shown an outstanding result in cancer treatment but these drugs suffer a lot of side effects, so there is a need to identify the novel phytochemicals that may have anti-EGFR activity. Methodology: The protein EGFR was retrieved from the PDB along with the hetero atoms attached with the crystal structure. The chosen 86 ginger compounds were downloaded from TIP database in 3D sdf format. Using the PyRx virtual screeing tool the target protein and ligand set were docked and then the Dockthor server was used to find docking score of the potential compounds. The docking score of all the compounds along with the standard compound, Erlotinib was obtained and analysed after the execution of docking program. Moreover, the Pharmacokinetic study was performed for the potential compounds. Results: The molecular docking study of our selected top compounds, TIP012988, TIP009544 and TIP013002 with higher binding affinity score than standard compound and good pharmacokinetic profile reveal that the selected ginger compounds are potent in obstructing the EGFR activity. Conclusion: The EGFR tyrosine kinase is found to be critical in the proliferation and metastasis of cancer. The identified top three ginger compounds through computational approaches exhibit higher potential in targeting EGFR activity in comparison to standard, Erlotinb, as the binding energy of the standard is less than the identified potential top three compounds. Moreover, the identified potential compounds possess good pharmacokinetic features indicating their characteristic of being safe for human consumption. The results obtained can be further validated through in-vitro approaches. The in-vitro validation is important as it will ensure that our findings are fruitful and synergetic for the cancer patients who possess EGFR lead cancer progression. Enhancing synergy with EGFR inhibitors and optimizing drug delivery could improve efficacy, leading to potential preclinical and clinical development of plant-derived EGFR-targeted cancer therapies.