| 초록 |
One of the most prevalent antiviral drugs is the oseltamivir (Tamiflu) that inhibits neuraminidase, which is the key enzyme for infection of the influenza virus. However, oseltamivir-resistant neuraminidase mutants have recently been found from humans, and their crystal structures were also identified. The objective of this research is to elucidate the mechanism of the resistance at the molecular level in order to design enhanced inhibitors against the mutant virus. For this purpose, the binding free energies of oseltamivir with the wild type neuraminidase and with His274Tyr neuraminidase known to be highly resistant to the oseltamivir were calculated by molecular dynamics simulation. The non-bonded interaction energies between the oseltamivir and active site residues were also calculated to investigate the contribution of non-bonded interaction to the total biding energy. Examining the effect of the mutation on the binding affinity elucidates the mechanism of resistance. |
