## 5 Conclusions  
Currently, there is no satisfactory therapy for HBV infection and HCC. The present study identified a group of druggable and nontoxic phytocompounds from herbs modulating the therapeutic targets involved in HBV infection and HCC through in silico techniques involving compound-protein pathway enrichment analysis coupled with network pharmacology, molecular docking, and dynamics simulation studies. Results of this study suggest that flavonoid and a diterpenoid fraction of _A. paniculata_ and flavonoid fraction of _T. populnea_ could be potent as a combined therapy for the treatment of patients with HBV infection and its associated HCC without expecting adverse drug reactions. Theoretical and predicted knowledge generated in this study needs to be further confirmed using in vitro studies including in viral cell lines and animal models. **Supplementary Materials:** The following are available online at [[https://www.mdpi.com/article/10.3390/app122110691/s1](https://www.mdpi.com/article/10.3390/app122110691/s1)]([https://www.mdpi.com/article/10.3390/app122110691/s1](https://www.mdpi.com/article/10.3390/app122110691/s1)), Table S1: List of references for the selected medicinal plant for the treatment of hepatitis-like illness including jaundice, hepatitis, fever, inflammation and for hepatoprotective and antiviral potential; Table S2: List of plants with their phytocompounds and druglikeness properties; Table S3: Toxicity profile of phytocompounds; Table S4: Overall probable targets modulated by phytocompounds (Predicted using BindingDB); Table S5: Gene Ontology (GO) functional enrichment analysis: regulated molecular functions of 16 protein targets modulated by the phytocompounds; Table S6: GO process enrichment analysis: molecular processes of 16 protein targets modulated by phytocompounds. Table S7: Pathway enrichment analysis: 16 protein targets modulated by 139 pathways, Table S8: Role of 16 protein targets in the pathogenesis of hepatitis B viral infection and hepatocellular carcinoma (HCC); Table S9: Interaction of phytocompounds with protein targets and pathways and Edge Count w.r.t. protein target. Figure S1: Venn diagram representing the modulated protein targets involved in HBV-induced HCC by the phytocompounds from _Andrographis paniculata_ and _Thespesia populnea_; Figure S2. WT- EGFR model 30. (a) Ramachandran plot for amino acid distribution (b) PyMOL superimposed (Red: Template (PDB file 4I23) and Blue: Model 30), (c) Clustal W template and model 30 alignment; Figure S3. WT-EGFR model-30 RMSD plot showing the deviation and minimum energy conformation observed at 45,252.0 thps (\(-\)129,809.51 kcal/mol). **Author Contributions**: Methodology, Validation, Formal analysis, Investigation, Data curation, and Writing--original draft, V.S.P. ; Conceptualization, Resources, Writing--original draft, Writing--review and editing, Supervision, Project administration, and Funding acquisition, D.R.H. ; Formal analysis, Co-supervision, Writing--review and editing, U.V. ; Data curation, review and editing, S.H.D. and P.K. ; Resources, Writing--review and editing, and Funding acquisition, H.V.H. and S.R. Supervision and Writing--review and editing, S.S.J. All authors have read and agreed to the published version of the manuscript. **Funding:** This study was funded by the Indian Council of Medical Research, Department of Health Research, New Delhi (ICMR grant no. ISRM/12(61)2019) and ICMR-National Institute of Traditional Medicine, Belagavi, India. **Institutional Review Board Statement**: Not applicable. **Infrared Consent Statement**: Not applicable. **Data Availability Statement**: The authors confirm that the data supporting the findings of this study are available within the article and/or its Supplementary Materials. **Acknowledgments**: The authors gratefully acknowledge the extramural funding of the Indian Council of Medical Research, Department of Health Research, New Delhi, and the Bioinformatics center of ICMR-NITM for providing resources.