In Silico Analysis of Possible Interaction between Host Genomic Transcription Factors (TFs) and Zika Virus (ZikaSPH2015) Strain with Combinatorial Gene Regulation; Virus Versus Host—The Game Reloaded

Abstract

In silico analysis is a promising approach for understanding biological events in complex diseases. Herein we report on the innovative computational workflow allowed to highlight new direct interactions between human transcription factors (TFs) and an entire genome of virus ZikaSPH2015 strain in order to identify the occurrence of specific motifs on a genomic Zika Virus sequence that is able to bind and, therefore, sequester host’s TFs. The analysis pipeline was performed using different bioinformatics tools available online (free of charge). According to obtained results of this in silico analysis, it is possible to hypothesize that these TFs binding motifs might be able to explain the complex and heterogeneous phenotype presentation in Zika-virus-affected fetuses/newborns, as well as the less severe condition in adults. Moreover, the proposed in silico protocol identified thirty-three different TFs identical to the distribution of TFBSs (Transcription Factor Binding Sites) on ZikaSPH2015 strain, potentially able to influence genes and pathways with biological functions confirming that this approach could find potential answers on disease pathogenesis.

Cheminformatics and Pharmacological Network Analysis for the Prediction of Molecular Mechanism of Herbal Drug Ligands

“…Further, the speci c molecular docking studies comprising interaction analysis (protein-ligand), replica exchange molecular dynamics (REMD), MM-GBSA, and APBS electro statistics which is validated by Ramachandran torsion plots, this approach may be applied to calculate forces, energies, and binding a nity [9]. These scienti c efforts will not only improve the biological e cacy of the current drug but also provide a roadmap for innovative drug development or a fair potential for drug reuse after pathways are revealed at the genomic level [10]. Furthermore, it may be assumed that there is a wide scope for investigation of other members of the Cyperaceae family including Scirpus grossus L., Trichophorum clintonii (Gray) S.G.., and Eleocharis dulcis (Burm.f.)…”

“…The ligands (bioactive component, scaffold analog) of Cyperus rotundus L. were evaluated to nd its molecular activities at different target sites by maintaining a curative space for drug discovery, drug reuse[8], development, advancement, and innovative results [9]. These efforts include an in silico approach to cheminformatics [10], and proteogenomic analysis [11] including physicochemical analysis, pharmacokinetics, pharmacodynamics, medicinal chemistry, drug similarities, designing of novel scaffolding analog, target predictions, molecular docking, identi cation of genes, genomic interactions, cellular signaling, and their biological insights (top ten diseases/ disorders regulated by these interactive genes via identifying the target sites of ligands) through representative overexpression analysis (ORA) [12], and Network Topology-based Analysis (NTA) [13]. The topological polar surface area (TPSA) of a molecule is de ned as the surface sum of all polar atoms or molecules including oxygen, nitrogen, and their attached hydrogen atoms [5].…”