Zanamivir analogues are designed to improve the therapeutic use. Replacing the carboxylate group at the C1 to phosphonate group led the drug to be more potent with high affinity to form ionic interaction with the active site. Additionally, the click-chemistry reaction was used to synthesize the C4-triazole-modified zanamivir analogue that shows inhibitory activity close to zanamivir. Laninamivir is designed by replacing C7 hydroxy moiety with small lipophilic group, -OCH3, which resulted in an excellent inhibitory activity. The C8 and C9 diol play an important role in the binding affinity with neuraminidase, prolonging the effect. The polymer scaffolds at the C7 position of zanamivir via an alkyl ether has gained more attention as this showed enhanced antiviral activity.