1st International and 10th National Iranian Conference on Bioinformatics

Drug design against influenza pH1N1 polymerase through computational biology and molecular modeling

Paper ID : 1306-ICB10

Authors:

atousa moradzadegan *

Abstract:

Influenza H1N1 virus is the main cause of worldwide epidemics and annual influenza outbreaks in humans. But few drugs are available for its treatment. Consequently, researchers have been engaged in efforts to discover new antiviral mechanisms that can lay the foundation for novel anti-influenza drugs. The antiviral drugs that selectively act on RNA polymerase are less prone to resistance and possess fewer side effects on the patient. Therefore, there is increased interest in screening compounds that can inhibit influenza virus RNA polymerase. The viral RNA polymerase is comprised of subunits PA, PB1 and PB2. PA has endonuclease activity and is a common target for drug design. In this study, we employed molecular docking, molecular dynamics (MD), MMPBSA and ADME studies to detect and propose an inhibitor among 11873 structures against PA. Our molecular docking, MD and MMPBSA studies showed that ZINC15340668 has ideal characteristics as a potent PA inhibitor and can be used in experimental phase. Also, ADME prediction showed that all physic-chemical parameters are within the acceptable range defined for human use. Molecular mechanism based study revealed that upon inhibitor binding; the flexibility of PA backbone is enhanced. This observation demonstrates the plasticity of PA active site, and it should be noted in drug design against PA Influenza A viruses.

Keywords:

Influenza H1N1, Endonuclease, Molecular docking, Molecular dynamics, ADME prediction

Status : Paper Accepted (Poster Presentation)