In Silico Analysis of the Apoptotic and HPV Inhibitory Roles of Some Selected Phytochemicals Detected from the Rhizomes of Greater Cardamom

Abstract

Occurrence of cervical cancer, caused due to persistent human papilloma virus (HPV) infection, is common in women of developing countries. As the conventional treatments are expensive and associated with severe side effects, there is a need to find safer alternatives, which is affordable and less toxic to the healthy human cells. Present study aimed to evaluate the anti-HPV and apoptotic potential of four compounds from the greater cardamom ( Amomum subulatum Roxb. var. Golsey), namely rhein, phytosphingosine, n-hexadecenoic acid and coronarin E. Their anti-HPV and apoptotic potential were studied against viral E6, E7 and few anti-apoptotic proteins of host cell (BCL2, XIAP, LIVIN) by in silico docking technique. Phytochemicals from the plant extract were analysed and identified by LC/MS and GC/MS. Involvement of the target proteins in various biological pathways was determined through KEGG. Structural optimization of the three-dimensional structures of the ligands (four phytochemicals and control drug) was done by Avogadro1.1. Receptor protein models were built using ProMod3 and other advanced tools. Pharmacophore modelling of the selected phytochemicals was performed in ZINCPharmer. Swiss ADME studies were undertaken to determine drug likeness. The ligands and proteins were digitally docked in DockThor docking program. Protein flexibility-molecular dynamic simulation helped to study protein–ligand stability in real time. Finally, the correlation of evaluated molecules was studied by the use of principal component analysis (PCA) based on the docking scores. All the ligands were found to possess apoptotic and anti-cancer activities and did not violate Lipinsky criteria. n-Hexadecanoic acid and its analogues showed maximum efficacy against the target proteins. All the protein–ligand interactions were found to be stable. The uncommon phytochemicals identified from rhizomes of greater cardamom have anti-cancer, apoptotic and HPV inhibitory potentials as analysed by docking and other in silico studies, which can be utilized in drug development after proper experimental validation. Supplementary Information The online version contains supplementary material available at 10.1007/s12010-022-04006-3.

An in-silico pharmacophore-based molecular docking study to evaluate the inhibitory potentials of novel fungal triterpenoid Astrakurkurone analogues against a hypothetical mutated main protease of SARS-CoV-2 virus

“…surface area) model, XlogP3 is an automistic method with correction factors [ 95 ]. All the molecules except for Astrakurkurone passed iLogP and XlogP3 criteria (range iLOGP: 0.19 to 4.37 and XlogP3: 1.48 to 6.19) [ 36 , 96 ]. All compounds were found to be water soluble (LogS).…”

“…PCA aids in the clustering of the given dataset based on the variables [ [97] , [98] , [99] , [100] ]. In our previous studies, we successfully employed the PCA tool as the primary step to cluster the compounds, thereby understand the mechanism of ligand-protein molecular interaction [ 36 , 101 ]. Similar to these studies, we found four clusters (C1–C4) in the PCA analysis.…”

“…Among the projected Principal components, PC1 represents the maximum variance of the dataset [ 67 , 68 ]. Minitab software was used to perform Principal Component Analysis (PCA), to statistically cluster phytocompounds based on their binding affinities as described in our earlier study [ 36 ]. Briefly, molecular docking affinity data (Kcal mol −1 ) was used as inputs for the analysis.…”

“…Recent studies also indicated a similar trend towards COVID-19 research [ [31] , [32] , [33] , [34] ]. In our previous studies, we tested various phytochemicals including curcumin as the antiviral agents against SARS-CoV-2 [ [35] , [36] , [37] ] studied the effect of isolated phytochemicals from Helichrysum bracteatum against the viral protein M pro . In a similar study, Ristovski et al (2022) [ 38 ] showed biflavonoids and tannins as the major class of compounds optimally targeting M pro .…”

Exploring the inhibitory potential of Nigella sativa against dengue virus NS2B/NS3 protease and NS5 polymerase using computational approaches

“…RMSF values are utilized to calculate the atomic positional variation of each residue based on its C-alpha (Ca) atom. 72,73 The complexes NS2BNS3-taraxerol and NS5-apigenin under iMODS investigation have a signicant amount of deformability, according to the normal mode analysis. The low eigenvalue, covariance map, and elastic network of the complex under study are indications of the molecule's potential deformability and allowable dynamics.…”