Investigating the effects of four medicinal plants against dengue virus through QSAR modeling and molecular dynamics...

The Dengue virus (DENV) has been increasingly recognized as a prevalent viral pathogen responsible for global transmission of infection. It has been established that DENV's NS5 methyltransferase (MTase) controls viral replication. As a result, NS5 MTase is considered a potentially useful drug target for DENV. In this study, the two phases of virtual screening were conducted using the ML-based QSAR model and molecular docking to identify potential compounds against NS5 of DENV. Four medicinal plants [Aloe vera, Cannabis sativa (Hemp), Ocimum sanctum (Holy Basil; Tulsi), and Zingiber officinale (Ginger)] that showed anti-viral properties were selected for sourcing the phytochemicals and screening them against NS5. Additionally, re-docking at higher exhaustiveness and interaction analysis were performed which resulted in the identification of the top four hits (135398658, 5281675, 119394, and 969516) which showed comparable results with the control Sinefungin (SFG). Post molecular dynamics simulation, 135398658 showed the lowest RMSD (0.4-0.5 nm) and the maximum number of hydrogen bonds (eight hydrogen bonds) after the control while 5281675 and 969516 showed comparable hydrogen bonds to the control. These compounds showed direct interactions with the catalytic site residues GLU111 and ASP131, in addition to this these compounds showed stable complex formation as depicted by principal component analysis and free energy landscape. 135398658 showed lower total binding free energy (ΔG_Total = -36.56 kcal/mol) than the control, while 5281675 had comparable values to the control (ΔG_Total = -34.1 kcal/mol). Overall, the purpose of this study was to identify phytochemicals that inhibit NS5 function, that could be further tested experimentally to treat dengue virus (DENV).