Screening and selection of a lead phytochemical inhibitor against Nsp3 protein, from Lawsonia inermis L. through in silico approaches

Lawsonia inermis L., a plant of immense significance as the natural source of dye “Mehendi” is rich in secondary metabolites that impart important medicinal properties. These phytochemicals offer plant-based alternatives to synthetic drugs, which are often associated with harmful side effects, reinforcing the need to explore such natural compounds. The main objective of this study is to find plant-based lead from among the phytochemicals present in Lawsonia inermis L., against Nsp3 protein. Methanolic extracts from the plant was used and a group of phytochemicals were verified and identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, which were then subjected to phytochemical screening. The shortlisted best ligands (caffeic acid and lawsone) were subjected to molecular dynamic simulations for 100 ns, where RMSD, Rg and RMSF were analysed along with the binding affinities to the protein. Lawsone and caffeic acid emerged as good candidates. Molecular dynamic simulations indicated that lawsone, a naphthoquinone, formed stable complexes with Nsp3, exhibiting favourable RMSD, RMSF and Rg values, as well as a strong binding affinity of -20.72 kcal/mol. Our analysis shows the prospective possibility of lawsone, as a potential antiviral compound. This also highlights the interactions of a naphthoquinone, against Nsp3 protein, increasing the medicinal importance of the plant. Previous studies usually reveal phenols and flavonoids to be effective antiviral agents. This study, for the very first time, reveals the potential of lawsone (naphthoquinone and the main pigment of the plant), against Nsp3 protein.