Implications of protein conformations to modifying novel inhibitor Oseltamivir for 2009 H1N1 influenza A virus by simulation and docking studies.

Recently three FDA approved existing drugs, namely-Oseltamivir, Peramivir and Zanamivir, used against Neuraminidase (NA) for the inhibitory effect on the process of viral progeny release to inhibit infection. All NA subtypes has been divided into two groups (Group 1 and Group 2) based on phylogenetic study. Oseltamivir and Zanamivir drugs are designed for Group 2 NA but are also used against 2009 H1N1 NA that lies in Group 1. There is no specific drug available for H1N1 and, consequently, there is an urgent requirement for the same. The structure-based drug design and fragment-based drug design methods are used for building more effective and economic drug molecules. In this work, the fragment-based drug development followed by fragment evolution on the basis of protein conformations after every 10 ns of 100 ns simulation. There are two analogs of Oseltamivir acid drug discovered in this study. Only analog 1, along with Oseltamivir acid, were then docked with the native protein. The analog 1 (benzoic acid inhibitor 11) exhibited higher binding affinity value of - 10.70 kcal/mol in comparison to its predecessor. The concept of conformations and protein-ligand interactions can be useful in designing new drugs for H1N1 with high specific binding.