## 3 Results
### Network Analysis  
Network analysis identified Skullcapflavone I, Wightin, 2'-hydroxy-5,7,8-trimethoxyflavone, Altisin, Andrographiside, 5-Hydroxy-7,8,2'-trimethoxyflavone,5-hydroxy-7,8,2',3',4'-pentamethoxyflavone, 5-hydroxy-7,8,2',5'-tetramethylflavone, 5,4'-dihydroxy-7,8,2',3'-tetramethoxyflavone, Andrographidine C, Wightin, 5-hydroxy-7,8-dimethoxyflavone, 5-hydroxy-7,8,2',3'-TetramethoxyflavoneandPaniculideB from _Andrographis paniculata_ (whole plant); Herbacetin, Gossypetin, Kaempfer-7-Glucoside from _Thesespia populnea_ (Flowers); Isornhametin from _Aerva lanta_ (Aerial part); and Pinnatin from _Pongamia pinnuta_ (Seed) to have highest edge count. Further, among 14 pathways, EGFR tyrosine kinase inhibitor resistance, hepatitis B, and hepatocellular carcinoma pathways were identified as enriched pathways via modulating EGFR, AKT1, BCL2, HGF, IGF1R, MAP2K1, MAPK1, PRKCA, PRKCB, PRKCG, STAT3, CDK2, CDK6, STAT3, TNF, and TERT as common target proteins (Tables 2 and 3). However, the above-selected compounds were considered based on polypharmacology therapy due to their probable affinity toward multiple targets and pathways. The herb-compound-protein pathway network is shown in Figure 3. For further docking studies, based on the polypharmacology analysis, phytocompounds that are predicted to modulate multiple protein targets and pathways were selected; therefore, 11 phytocompounds from _Andrographis paniculata_ were predicted to target 13 protein molecules and 3 phytocompounds from _Thesespia populnea_ were predicted to target 8 protein molecules involved in HBV-induced HCC and are repre \begin{table}
\begin{tabular}{l l l l l} \hline
** KEGG ID** & **Pathway Name** & **Gene Count** & **False Discovery Rate** & **Modulated Gene within a Pathway** \\ \hline hsa05161 & Hepatitis B & 11 & 1.07E-18 & MAPK1, PRKCA, PRKCB, PRKCG, \\  & & & & STAT3, TNF \\  & & & & AKT1, CDK6, EGFR, HGF, IGF1R, \\ hsa05225 & Hepatocellular carcinoma & 11 & 3.43E-18 & MAPK1, PRKCA, PRKCB, \\  & & & & PRKCG, TERT \\ hsa01521 & EGFR tyrosine kinase & 11 & 6.37E-21 & MAPK1, PRKCA, PRKCB, \\  & & & & PRKCG, STAT3 \\ hsa05206 & MicroRNAs in cancer & 9 & 2.07E-14 & BCL2, CDK6, EGFR, MAPK1, \\  & & & & PRKCA, PRKCB, PRKCG, STAT3 \\ hsa04010 & MAPK signaling pathway & 10 & 7.51E-14 & AKT1, EGFR, HGF, IGF1R, MAP2K1, \\  & & & & MAPK1, PRKCA, PRKCB, PRKCG, TNF \\ hsa04151 & PI3K-Akt signaling pathway & 10 & 3.22E-13 & AKT1, BCL2, CDK2, CDK6, EGFR, \\  & & & & IGF1R, MAPK1, MAPK1, \\ hsa04014 & Ras signaling pathway & 9 & 5.60E-13 & AKT1, EGFR, HGF, IGF1R, MAP2K1, \\  & & & MAPK1, PRKCA, PRKCB, PRKCG \\ hsa04150 & mTOR signaling pathway & 8 & 1.52E-12 & AKT1, IGF1R, MAP2K1, MAPK1, \\  & & & & PRKCA, PRKCB, PRKCG, TNF \\ hsa04210 & Apoptosis & 5 & 2.18E-07 & AKT1, BCL2, MAP2K1, MAPK1, TNF \\ hsa05203 & Viral carcinogenesis & 5 & 8.12E-07 & CDK1, CDK2, CDK6, MAPK1, STAT3 \\ hsa04668 & TNF signaling pathway & 4 & 3.85E-06 & AKT1, MAPK1, TNF \\ hsa04630 & Jak-STAT signaling pathway & 4 & 1.57E-05 & AKT1, BCL2, EGFR, STAT3 \\ hsa04115 & p53 signaling pathway & 3 & 4.58E-05 & CDK1, CDK2, CDK6 \\ hsa04110 & Cell cycle & 3 & 0.00021 & CDK1, CDK2, CDK6 \\ \hline \end{tabular}
\end{table} 
Table 3: Pathways involved in HBV infection and associated hepatocellular carcinoma modulated by the phytocompounds. sented in a Venn diagram (Figure S1). Phytocompound-affected checkpoints within the Hepatitis B infection pathway (hsa05161) were traced from the KEGG pathway and are represented in Figure 4.  
Further, the study was extended to molecular docking and dynamics simulations. As discussed earlier, EGFR was chosen as the most potential target, as it was found to be the highly connected protein target within the network and is also a well-known therapeutic target in many types of cancer, viz., lung cancer [36], glioblastoma [37], breast carcinoma [38], HCC [39; 40], and so on. In this study, EGFR was found to be involved in hepatocellular carcinoma, MAPK, PIJK-Akt, Jak-STAT, and Ras signaling pathways, and the EGFR tyrosine kinase inhibitor resistance pathway.