Exploring the Molecular Mechanism of Action Between Drug and RNA Polymerase Based on Partially-Resolved Spatial Structures

Title:Exploring the Molecular Mechanism of Action Between Drug and RNA Polymerase Based on Partially-Resolved Spatial Structures

Volume: 9 Issue: 4

Author(s): Yajun Sheng, Chen Zhang, Xingye Qiu, Wei Zheng, Jishou Ruan and Yiming Shao

Affiliation:

Keywords: Combination of drug and drug, drug resistance, non covalent bonds, target pocket, universal drug.

Abstract: The RNA polymerase of Influenza A virus (IAV), which is comprised of three units PA, PB1 and PB2, is involved in transcription and replication of the influenza virus. In order to develop effective treatment for IAV, researchers have focused on designing drugs targeting IAV polymerase. Currently, crystal structures of the IAV polymerase PA-PB1, PB1-PB2 complexes and the PA subunit have been obtained by several groups, providing useful information regarding potential binding sites in drug design. However, to gain full understanding of the molecular mechanism of IAV polymerase in viral transcription and replication, thereby aiding drug development, a complete atomistic structure of the RNA polymerase is required. In this paper, we employed computer-aided drug design tools to describe the complete structure of the RNA polymerase and proposed a putative mechanism. We predict that the combination of Vancomycin and Oseltamivir will be an effective drug to universally treat IAVs with no resultant drug resistance if this putative mechanism is true.

Cite this article as:

Sheng Yajun, Zhang Chen, Qiu Xingye, Zheng Wei, Ruan Jishou and Shao Yiming, Exploring the Molecular Mechanism of Action Between Drug and RNA Polymerase Based on Partially-Resolved Spatial Structures, Current Computer-Aided Drug Design 2013; 9 (4) . https://dx.doi.org/10.2174/15734099113099990025