Ebola virus is a single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever. The outbreak of Ebola infections in West Africa during 2014 has expanded exponentially with a doubling period of 34.8 days, resulting 83% mortality rate as it exhibited resistance to large number of anti-viral drugs. As there are no valid drugs to treat Ebola virus infections that cause severe hemorrhagic fever, the urgency in search and design of utmost anti-viral drug has propelled our research to screen the compounds to inhibit the Ebola infections. Thus in our present study, the membrane-associated major matrix protein (VP40) that plays a central role in the formation of filamentous virus particles and also binds to RNA tribonucleotide to form the viral matrix is chosen as potential drug target. Blocking the RNA site of interaction with VP40 may restrict the pathway of virus membrane formation. Hence the known anti-viral drugs were screened for their inhibitory activity by docking in the RNA binding site of VP40. The result of virtual screening revealed that all the compounds screened exhibited the encouraging docking scores. The highest docking score was observed for Nocodazole, which suggests that this compound might effectively occupy the RNA binding regions; the results of these binding interactions indicate that the most important amino acids in the binding site of VP40 are to be considered while designing the novel anti-viral drugs that can effectively inhibit the Ebola infections.