Computational Analysis of Andrographolide and Berbamine for Targeting Glioblastoma Associated with Viral Infections

Glioblastoma (GB) patients are prone to developing viral infections pertaining to a weakened immune system. Coronavirus disease 2019 (COVID-19), Cytomegalovirus (CMV) infection and Human Papillomavirus (HPV) infection have shown evidence to co-occur with GB individually. The combination of andrographolide and berbamine has previously been shown to synergistically inhibit the growth of GB. In this study, the common protein targets were identified for viral infections and GB and the identified phytocompounds interacting with the same targets was studied by bioinformatics and network pharmacology. To validate the targets of andrographolide and berbamine against GB-viral co-occurrence, a variety of open-source datasets and a Venn Diagram tool were used. Several molecular mechanisms were identified against GB and viral comorbidities (SARS-CoV-2, CMV, and HPV) by using several bioinformatic tools. Six common critical targets and 41 transcription factors have been identified using Venny 2.0. The critical targets were found to be enriched in pathways like EGFR tyrosine kinase inhibitor resistance, ErbB signaling pathway, which are necessary for GB targeting. Berbamine and andrographolide indicated potential as therapeutic agents for glioblastoma, particularly in the context of co-infection with the studied viral diseases. The regulation of important targets (SRC, ERBB2, PRKCA, LYN, KDR, ABL1) and the ERK1 and ERK2 cascade seems to be connected to the underlying mechanisms. The study paves the way for developing novel treatments targeting glioblastoma and its associated viral comorbidities.