Identification of selective influenza viral sialidase inhibitors is highly desirable in order to minimize or avoid the adverse effects due to the possible inhibition of endogenous human sialidases. We recently reported the evaluation of C9 N-acyl Neu5Ac2en mimetics as probes for human sialidases. Herein, we describe the in vitro activity of the same set of C9 N-acyl Neu5Ac2en mimetics against sialidases expressed by influenza virus A/PR/8/34 (H1N1), A/Memphis/1/72 (H3N2), and A/Duck/313/78 (H5N3) strains. Compound 8 is identified as a promising starting point for the development of viral sialidase selective inhibitors. Multiple sequence alignment and molecular docking techniques are also performed to explore the plausible interaction of compound 8 with viral sialidases. 1. Introduction Influenza is a perceivably benign condition that develops in approximately 20% of the world's population and kills 0.25 to 0.5 million people every year worldwide, according to the WHO [1]. Influenza can cause a high level of mortality, particularly in children, elderly, or those with chronic underlying conditions of lung, heart, kidney, and so forth [2]. There have been three influenza pandemics in the 20th century, and this has lead to millions of deaths with the appearance of a new strain of the virus in each pandemic [3, 4]. Since June 11, 2009, a new strain of swine-origin influenza A virus subtype H1N1 has been declared as the first global influenza pandemic of the 21st century. As of July 4, 2010, over 18311 deaths in more than 214 countries have been confirmed (http://www.who.int/csr/don/2010_07_09/en/index.html). Influenza viruses belong to the Orthomyxoviridae family and are divided into three types, namely, A, B, and C. Influenza A virus, in particular, represents a significant health risk to the public due to both its ability to spread rapidly among humans and being associated with major epidemic outbreaks [5]. Influenza virus is an enveloped virus containing eight segmented, single (nonpaired), and negative sense RNA strands that code for 11 proteins [6, 7], including two glycoproteins (hemagglutinin (HA), neuraminidase (NA) (also known as sialidase), two matrix proteins (M1 and M2), two nonstructural (NS) proteins (NS1 and NS2), nucleoprotein (NP), two polymerase basic proteins (PB1 and PB2), polymerase acidic protein (PA), and basic polymerase 1 frame 2 protein (PB1-F2). Viruses of the influenza type A are subtyped based on the HA and NA, antigenic surface glycoproteins found on the viral envelope, which are essential for viral entry and replication in the
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