Docking-based workflow and ADME prediction of some compounds in Curcuma longa and Andrographis paniculata as polymerase PA-PB1 inhibitors of influenza A/H5N1 virus

Authors:
  • SCSitti Nur Aidah Lya Citra
    Sitti Nur Aidah Lya Citra
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Abstract
Influenza is an infectious disease of the respiratory system caused by the influenza virus. Influenza virus RNA polymerase (RdRp) is essential in viral RNA replication and transcription. This polymerase has acid polymerase (PA) and polymerase basic 1 (PB1) subunits responsible for viral endonuclease and proteolytic activity. This study aims to determine the potential and interactions of the biochemical constituents of turmeric (Curcuma longa) and bitter (Andrographis paniculata) against the polymerase PA-PB1 (PDB ID: 3CM8) from the influenza A virus. The study was carried out using the molecular docking workflow method with a combination of standard-precision (SP), extraprecision (XP), and induced fit docking (IFD) utilizing the Maestro's Schrodinger. The docking result successfully identified seven compounds in C. longa and thirty-four in A. paniculata, which had a better docking score than R151785 as a reference ligand. XP docking showed compounds 1 from C. longa with a score of-7.555 kcal/mol and 4 from A. paniculata with a score of-9.156 kcal/mol. The IFD method results identified compounds 3 from C. longa and 5 from A. paniculata as potential compounds in inhibiting the activity of the polymerase PA-PB1 with a docking score of-9.979 kcal/mol, and-13.153 kcal/mol, respectively. All the best compounds interacted with critical residues such as Thr7, Gln16, Gln587, Ser594, Lys643, Ser647, Ser659, Ser662, Arg663, and Asn703 of the polymerase PA-PB1 enzyme from influenza A virus. The best compound in turmeric showed an excellent GI absorption profile, and the best compound in bitter showed a good safety profile because it was predicted to only inhibit the CYP3A4 enzyme. All the best compounds from these two plants fulfilled the criteria for oral drugs based on Lipinski's rules. Based on the research, these two plants have a potential antiviral activity to be verified experimentally as a candidate for Influenza A virus inhibitor.

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