Authors suggested that it M344 might be possible to design new high affinity inhibitors that exploit the size and the conformation of the group-1 cavity [9]. Moreover, the identification of strains that are resistant to existing NA inhibitors, such as the oseltamivir-resistant variants of the viruses H1N1 and H5N1 [3], highlights the need to design new specific drug candidates for the N1 subtype.
In order to search for new compounds that specifically fit the group-1 neuraminidase, making interactions with both the 150-cavity and the active site, we have performed a large scale docking simulation to evaluate the binding affinity of a set of about 2000 ligands for the open and closed structure of N1. For taxonomy purpose we have implemented a virtual screening pipeline that includes docking simulations, interaction analysis and a multi-filtering procedure to select compounds with high binding efficiency and target-specific interaction properties. Two of the selected ligands are illustrated in detail and are employed as substituent to design oseltamivir derivatives which can be proposed as candidates for experimental tests.
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Introduction Tumor stage remains one of
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