The　DENV-NS5　RNA-dependent　RNA　polymerase　(RdRp)　is　essential　for　viral　replication,　and　one　of　the　targets　of　anti-virus.　In　this　study,　the　Uni-VSW　module　was　used　to　virtual　screen　1.6　million　compounds　in　the　ChemDiv　and　TargetMol　(USA)　database,　27　candidates　were　obtained.　Thereby　23　candidates　were　selected　based　on　their　binding　free　energies　by　50　ns　MD　simulations.　The　biological　activity　of　the　candidates　and　the　reference　compounds　(BCX4430　and　Compound　27)　were　evaluated　on　their　IC50　values　against　DENV-NGC,　CC50　values,　and　selectivity　index.　Among　these,　the　IC50　values　of　D1　and　D8　were　13.06　+/-　1.17　mu　M　and　14.79　+/-　7.76　mu　M,　respectively,　which　were　better　than　that　of　Compound　27　(IC50　=19.67　+/-　1.12　mu　M).　The　comprehensive　MD　simulations　were　performed　on　the　candidates　to　assess　the　stability　behaviour　and　binding　mechanisms.　The　density　functional　theory　(DFT)　analysis　was　also　conducted　to　explore　the　structural　and　electronic　properties.