A Critical Prospect of Structural Designing of Avian Influenza A/H5N1 Neuraminidase Inhibitors That Evade Tamiflu Resistance

The key public health concern is to define the way in which the next influenza pandemic will be controlled. At present, the question of vital importance is: in the absence of a specific avian flu vaccine, could antiviral drugs obstruct a pandemic should the virus spread from birds to humans? The answer to the issue is inevitably related to finding the ways to circumvent Tamiflu resistance that is well documented in the literature. Several remarkable but slightly mutually inconsistent contributions have been recently reported with the aim to facilitate the development of new inhibitors acting on the key target—neuraminidase of avian influenza A/H5N1 virus. Herein, the versatile arguments are critically analyzed and reconciled. Consequently, the most relevant structural basis for the rational design of novel antivirals is elaborated.