Infectious Spleen and Kidney Necrosis Virus (ISKNV) is linked to severe infections that cause significant financial losses in global aquaculture. ISKNV enters the host cell through its major capsid protein (MCP), and the resulting infection can lead to mass mortality of fish. Even though several drugs and vaccines are at various stages of clinical testing, none are currently available. Thus, we sought to assess the potential of seaweed compounds to block viral entrance by inhibiting the MCP. The Seaweed Metabolite Database (1110 compounds) was assessed for potential antiviral activity against ISKNV using high throughput virtual screening. Forty compounds with docking scores of ≥8.0 kcal/mol were screened further. The inhibitory molecules BC012, BC014, BS032, and RC009 were predicted by the docking and MD techniques to bind the MCP protein significantly with binding affinities of −9.2, −9.2, −9.9, and −9.4 kcal/mol, respectively. Also, ADMET characteristics of the compounds indicated drug-likeness. According to this study, marine seaweed compounds may operate as viral entrance inhibitors. For their efficacy to be established, in-vitro and in-vivo testing is required.