Bioinformatics approach for prediction and analysis of the Non-Structural Protein 4B (NSP4B) of the Zika virus.

BACKGROUND: The Nonstructural Protein (NSP) 4B of Zika virus of 251 amino acids from (ZIKV/Human/POLG_ZIKVF) with accession number (A0A024B7W1), Induces the production of Endoplasmic Reticulum ER-derived membrane vesicles, which are the sites of viral replication. To understand the physical basis of how proteins fold in nature and to solve the challenge of protein structure prediction, Ab-initio and comparative modeling are crucial tools. RESULTS: The systematic in silico technique, ThreaDom, had only predicted one domain (4 - 190) of NSP4B. I-TASSER, and Alphafold were ranked as the best servers for full-length 3-D protein structure predictions of NSP4B, where the predicted models were evaluated quantitatively using benchmarked metrics including C-score (-3.43), TM-score (0.77949), RMSD (2.73), and Z-score (1.561). The functional and protein binding motifs were realized using motif databases, secondary and surface accessibility predictions combined with Post-Translational Modification Sites (PTMs) prediction. Two highly conserved protein-binding motifs (Flavi NS4B and Bacillus papRprotein), together with three (PTMs) (Casein Kinase II, Myristyl site, and ASN-Glycosylation site) were predicted utilizing the Motif scan and Scanprosite servers. These patterns and PTMs were associated with NSP4B's role in triggering the development of the viral replication complex and its participation in the localization of NS3 and NS5 on the membrane. Only one hit from Structural Classification of Protein (SCOP) matched the protein sequence at positions 10 to 397 and was categorized six-hairpin glycosidases superfamily according to CATH (Class, Architecture, Topology, and Homology). Integrating this NSP4B information with the templates' SCOP and CATH annotations achieves it easier to attribute structure-function/evolution links to both previously known and recently discovered protein structures.

Nanomedicine as a putative approach for active targeting of hepatocellular carcinoma.

The effectiveness of chemotherapy in hepatocellular carcinoma (HCC) is restricted by chemo-resistance and systemic side effects. To improve the efficacy and safety of chemotherapeutics in HCC management, scientists have attempted to deliver these drugs to malignant tissues using targeted carriers as nanoparticles (NPs). Among the three types of NPs targeting (active, passive, and stimuli-responsive), active targeting is the most commonly investigated in HCC treatment. Despite the observed promising results so far, clinical research on nanomedicine targeting for HCC treatment still faces many challenges.These include batch-to-batch physicochemical properties' variations, limiting large scale production and insufficient data on human and environmental toxicities. This review summarized the characteristics of different nanocarriers, ligands, targeted receptors on HCC cells and provided recommendations to overcome the challenges, facing this novel line of treatment for HCC.