Currently not much is known about the H7N9 strain, and this is the major drawback for a scientific strategy to tackle this virus. Herein, the 3D complex structure of the H7N9 RNA-dependent RNA polymerase has been established using a repertoire of molecular modelling techniques including homology modelling, molecular docking, and molecular dynamics simulations. Strikingly, it was found that the oligonucleotide cleft and tunnel in the H7N9 RNA-dependent RNA polymerase are structurally very similar to the corresponding region on the hepatitis C virus RNA-dependent RNA polymerase crystal structure. A direct comparison and a 3D postdynamics analysis of the 3D complex of the H7N9 RNA-dependent RNA polymerase provide invaluable clues and insight regarding the role and mode of action of a series of interacting residues on the latter enzyme. Our study provides a novel and efficiently intergraded platform with structural insights for the H7N9 RNA-dependent RNA Polymerase. We propose that future use and exploitation of these insights may prove invaluable in the fight against this lethal, ongoing epidemic. 1. Introduction H7N9 is a serotype of the species Influenzavirus A that causes influenza in birds. Influenzavirus A, which is an enveloped virus, belongs to the family of Orthomyxoviridae, and kills more than 250,000 people worldwide every year on average. Its genome is comprised of eight negative sense, single-stranded RNA segments that encode eleven RNA proteins. A further classification of the influenza virus is based on two glycoproteins of its surface: the hemagglutinin (H) and the neuraminidase (N). There are 17 different hemagglutinin subtypes and 10 different neuraminidase subtypes. In February 2013, the novel avian-origin influenza A (H7N9) virus that emerged in Eastern China. H7N9 was first reported to have infected humans [1, 2]. The World Health Organization (WHO) was notified of illness onset between February 19 and March 15, 2013, when three human cases of influenza A (H7N9) were confirmed in Shanghai and Anhui. Five to ten days later, the patients developed severe pneumonia and progressive respiratory distress with lethal outcome. As of July 4, 2013, 133 documented human cases were confirmed and 43 cases ended in death (human infection with avian influenza A (H7N9) virus, 2013). Available evidence suggests that most people have been infected after having contact with infected poultry or contaminated environments [3]. Evolution of influenza viruses is mainly based on mutations and reassortments [4]. RNA segments frequently reassort when the same
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