The sialidase (neuraminidase, NA) of influenza virus plays a major role in the virus’ life cycle by facilitating release of virus progeny from the infected host cell.1 The enzyme has been successfully targetted in the development of anti-influenza therapeutics,2 with the potent and selective influenza NA inhibitors zanamivir 1 (Relenza™) and oseltamivir carboxylate 2 (Tamiflu™) currently on the market for treatment of influenza virus infection. However, the emergence of seasonal and pandemic influenza A H1N1 and avian H5N1 (‘bird flu’) viruses resistant to the most widely used drug Tamiflu,3 underscores the need for the development of next-generation anti-influenza drugs. Influenza A virus NAs can be divided phylogenetically into two groups, with recent structural studies4 showing that the two groups differ in the flexibility of the so-called ‘150-loop’. As a result of apparently greater flexibility in the 150-loop, group-1 NAs (including N1) present a more open active site architecture in the apo form compared to group-2 enzymes (including N2). This newly observed structural feature provides opportunities for new directions in anti-influenza drug design. Using a multidisciplinary approach, we have developed novel sialic acid derivatives of type 3, which bind the open 150‑loop form of group-1 NAs, and show selectivity in inhibition of N1 compared to N2 NA.5 This presentation will describe the design and development of this new class of influenza virus NA inhibitor.