Dengue fever, spread by mosquitoes, has emerged as one of the world's most significant infectious diseases. To replicate and generate more copies of itself inside the host cell, the virus needs its proteins. With the NS2B cofactor, the NS3 protease can convert the polyprotein into functional proteins. As a result, NS3 protease is an attractive target for researching and developing antiviral drugs to combat the dengue virus. So, To develop efficient antagonists against the NS2B/NS3 and NS1 protein, a comprehensive screening integrates ADMET properties, molecular docking, and QSAR investigation is carried out against NS2B/NS3 (PDB ID 3L6P) and NS1 (PDB ID 4O6B) for the potential targeted region. ADMET characteristics analysis was performed to screen (01- 09) antiviral polycyclic quaternary alkaloids (sanguinarine derivatives) to identify ligands that contravene absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters. From the outcome of the docking investigation, the binding energy is reported as -8.5 kcal/mole as the lowest and – 9.7 kcal/mole as the highest with NS2B/NS3 (PDB ID 3L6P) and -9.8 kcal/mole, -9.9 kcal/mole, -10.0 kcal/mole, -10.2 kcal/mole in ligands 06, 03,07 and 09 against NS1 (PDB ID 4O6B). It is noted that their solubility was determined to be moderate in the water system, and absorption rates were exceptionally high in the GI tract. None of the molecules were harmful to the liver (hepatotoxic) or skin sensitization. The predicted QSAR and pIC50 value and Lipinski rule are also accepted within the standard ranges. Therefore, the estimated in silico different biochemical score for the polycyclic quaternary alkaloid (sanguinarine derivatives) towards NS2B/NS3 (PDB ID 3L6P) and NS1 (PDB ID 4O6B) inhibitors suggests that these compounds could have a high level of efficacy.