Background: Bioactive compounds isolated from marine sponges such as the genera Haliclona and Pellina have garnered significant attention for their diverse pharmacological, have shown notable antiviral activities. This study employed molecular docking techniques to elucidate the potential interactions between 20 bioactive compounds from marine sponges and hepatitis C virus polymerase. Results from the molecular docking simulations provide valuable insights into the binding modes of manzamine A with the HCV polymerase receptor, exploring potential hydrogen bonding, hydrophobic interactions, and other molecular forces contributing to the stability of the ligand-protein complex. Methods: The retrieval and preparation of crystal structures or reliable models of HCV polymerase receptors as target proteins. The protein structures are optimized, and ligand-binding sites are identified. 20 Ligands were subjected to ligand preparation, ensuring its three-dimensional conformation is suitable for docking simulations. The docking studies, conducted using computational tools, focus on understanding the binding affinity, orientation, and potential interactions between 20 bioactive compounds and the target protein. Results: Among the compounds tested, manzamine A exhibited the most favorable binding affinity to the receptor, showcasing its superiority over the ribavirin antiviral drug. Conclusion: The comprehensive molecular docking analysis underscores the notable binding affinity of Manzamine A with the hepatitis C virus polymerase receptor, surpassing that of the ribavirin antiviral drug. The detailed insights provided into the structural interactions of manzamine A, ribavirin, and ligand 698 contribute to our understanding of potential antiviral mechanisms. These findings lay the groundwork for further experimental validations and highlight manzamine A as a promising candidate for future antiviral drug development.