Molecular Dynamic Investigation of H5N1 Influenza Virus Dual H274Y-I222K Mutation Resistance to Peramivir

In light of the rapid rise of an influenza pandemic, the constant genetic mutations of H5N1 influenza viruses pose a threat. Mutations at the sialic site are often responsible for multiple drug resistance. To design effective new inhibitors, it is necessary to undertake research into the mechanism of resistance of influenza viruses and their rapid mutations. The molecular dynamic simulation technique has been an instrumental tool in understanding how proteins function from an atomic perspective. A thorough investigation has not been conducted using molecular dynamics to examine the impact of these mutations (I222K, H274Y, and H274Y-I222K) on Peramivir. This study investigates the effects of I222K, H274Y, H274Y-I222K substitution on the neuraminidase–Peramivir complex and identifies responsible residues for complex conformations. The mutations caused distorted Peramivir orientation in the enzyme active site, which affected the inhibitor’s binding. In the presence of various mutations, interaction between protein and ligand became less thermodynamically favorable. We observed the following trend in binding free energy difference: WT更多