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Influenza virus transmission is largely mediated by its mutation and genome reassortment from distinct strains resulting in drug-resistances and pandemics. This necessitates the need for the discovery of more potential influenza inhibitors to prevent future epidemics. An in-silico approach was utilized here to design six new (21a-f) potential inhibitors of influenza neuraminidase (NA) using a hit compound 21 with good binding affinity, pre- dicted activity, and pharmacokinetic properties in our previous work. The modeled activities (pEC50) of the newly designed compounds (ranging between 8.188 and 7.600) were better than that of the hit compound 21 with predicted activity (pEC50) of 6.0101 and zanamivir (pEC50 of 5.6755) as the standard reference control used. The MolDock scores (ranging between-189.67 and 142.47 kcal/mol) of these newly designed compounds in the NA binding cavity were also better than the hit template 21 with a MolDock score of-125.33 kcal/mol and zanamivir standard drug (-136.36 kcal/mol). In addition, the conformational stability of the best-designed compound 21a in the NA binding cavity was further studied through the MD simulation of 100 ns. Moreover, the drug-likeness and ADMET predictions of these designed compounds showed their good oral bioavailability and pharmacokinetic profiling respectively. More so, the DFT calculations also revealed the relevance of these designed com- pounds in view of their smaller band energy gaps from the frontier molecular orbital calculations. This study could serve as a reliable in-silico perspective for the search and discovery of potential anti-influenza agents. [ABSTRACT FROM AUTHOR]