title: Exploring the molecular mechanism of action between drug and RNA polymerase based on partially-resolved spatial structures.
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.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Sheng
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Xingye
authors.initials: X
authors.lastname: Qiu
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Jishou
authors.initials: J
authors.lastname: Ruan
authors.affiliation: College of Mathematical Sciences and LPMC, Nankai University, Tianjin, PRC 300071, China. jsruan@nankai.edu.cn.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001665:Binding Sites; D017076:Computer-Aided Design; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D058990:Molecular Targeted Therapy; D053139:Oseltamivir / Q000008:administration & dosage / Q000494:pharmacology; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D014640:Vancomycin; D012321:DNA-Directed RNA Polymerases