Investigation about the Inhibition of HIV-1 Gp41 Fusion via Andrographis Paniculata: Virtual Screening, Molecular Dynamics Simulation and Free Energy Calculation

Laboratory of Biocrystallography and Computational Molecular Biology,Department of Physics, Periyar University, Salem-636 011, India

^*Corresponding Author

Poomani Kumaradhas

Professor and Head, Department of Physics

Periyar University, Salem-11, Tamilnadu

India

Email: kumaradhas@yahoo.com

Abstract

Andrographis Paniculata (AP) is well known for its antiviral and potential AIDS therapeutic property. Based on the experimental evidence we determined to find the potential molecule from AP against HIV-1 viral fusion. Hence the reported compounds present in the AP has been chosen for virtual screening and the results indicate that the molecules Bis-andrographolide ether and Beta-ducosterol forms required intermolecular interactions and have better binding affinity towards NHR of HIV-1 gp41 fusion inhibition. Further molecular docking, MD simulation, free energy calculations and ADME prediction have been carried out. The RMSD, RMSF, DSSP and PCA analysis reveals that mutation and binding mode of the molecules has high impact on the flexibility of gp41. Especially Intermolecular interactions and binding free energy values of these two molecules conveyed that the molecules will affect the viral fusion and six helix bundle formation. The ADME results proved their drug likeness properties. The present study indicates that the molecules can be the promising small molecule inhibitors of HIV-1 viral fusion and further drug designing

Keywords: Andrographis Paniculata, Wild and mutant NHR of gp41, MD simulation, Intermolecular interactions, Binding Free energy calculations

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