text: Zanamivir and Oseltamivir have been tested as hNEU inhibitors. Only Zanamivir shows moderate inhibition activity for hNEU. Isoenzyme selective inhibitors could potentially be very important. At present there are limited studies for the hNEU substrate specificity. DANA is a pan-selective inhibitor for all hNEU isoenzymes, with a difference from 2 to 10 fold inhibition activity, most effective for hNEU3 and hNEU4. Several reports have tested DANA-derivatives as inhibitors for hNEU2 and hNEU3. Most derivatives showed reduced inhibition in vitro. However, N5-azidoacetate-C9-azido derivative of DANA showed improved inhibition for hNEU2 and hNEU3. These studies concluded that the active site in the enzymes could tolerate large modifications at C9 better than at N5. Testing of C9 amido derivatives of DANA showed hNEU1-selective inhibitors. These compounds showed more activity then DANA and only minor activity for hNEU3 with around 25-fold selectivity for hNEU1. These studies show that the glycerol side-chain pocket in the active site can potentially be manipulated in the design of isoenzyme selective inhibitors for hNEU. A combination of C4 and C7 modified DANA derivatives has been reported with moderate selectivity for hNEU2 and hNEU3. Finally C9-triazole derivatives of DANA containing an alkoxy group with a nanomolar activity against hNEU4 isoenzyme have been reported. With a 500-fold selectivity for hNEU4, this is the highest reported selectivity for a hNEU isoenzyme to date.