A STUDY OF THE ACTIVE-SITE OF INFLUENZA-VIRUS SIALIDASE - AN APPROACHTO THE RATIONAL DESIGN OF NOVEL ANTIINFLUENZA DRUGS

The development of sialidase inhibitor-based potential anti-influenza drugs using rational drug design techniques has been of recent interes t. The present study details an investigation of the active site of in fluenza virus sialidase by using the program GRID in an attempt to des ign more potent inhibitors in the hope they will eventually lead to an ti-influenza drugs. A number of different probes (amino, carboxy, hydr oxy, methyl, etc.) have been used in an effort to determine the functi onal groups most likely to improve the binding of the starting templat e 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en). The data have correctly predicted the binding regions for the carboxylate, acet amido (NH and methyl), and glycerol (OH) groups of N-acetylneuraminic acid. Moreover, the data suggest that the addition of certain function alities (amino group) at the C-4 position should enhance the overall b inding.