| Popis: |
Background and Aim: Instances of chikungunya reported throughout the world in the past two decades of the present century. There is a lack of effective medicine or vaccine for chikungunya treatment. Non-structural protein, the nsP2 cysteine protease (nsP2pro) is an attractive target for inhibitors. It is a key enzyme for proteolytic cleavage of polyprotein precursors and produces functional proteins for replication and multiplication of the virus. Bioactive metabolites from Nigella sativa L; a popular spice and well-known medicinal plant, were selected for the current study against nsP2pro to search for potent non-toxic natural inhibitors of nsP2pro. Experimental procedure: Out of 54 bioactive metabolites from N. sativa 27 qualified drug likeliness properties. Virtual screening of 27 selected molecules was performed using AutoDock Vina. Top four molecules Kaempferol, (-)-Epicatechin, (+)-Catechin, and Apigenin with the least binding energy were taken for molecular docking employing AUTODOCK4. These metabolites were subjected to molecular dynamics simulation and MMPBSA, and the resilience of protein-ligand complexes had been assessed in terms of RMSD, RMSF, Rg, SASA, and hydrogen bonding. Results and Conclusions: Drug likeliness, molecular docking, molecular dynamics simulation properties, and MMPBSA analyses made clear that Kaempferol, (-)- Epicatechin, (+)- Catechin, and Apigenin all seem to be potential nsP2pro potent inhibitors and strong candidates for chikungunya virus drug development. |
