Comparative studies of the seven human coronavirus envelope proteins using topology prediction and molecular modelling to understand their pathogenicity

ABSTRACTHuman (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 are less virulent and cause mild, self-limiting respiratory tract infections, while SARS-CoV, MERS-CoV, and SARS-CoV-2, are more virulent and have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoVs infections, may provide insight into this disparate severity of the disease. Topology prediction programs and 3D modelling software was used to predict and visualize structural aspects of the hCoV E protein related to its functions. All seven hCoV E proteins largely adopted different topologies, with some distinction between the more virulent and less virulent ones. The 3D models refined this distinction, showing the PDZ-binding motif (PBM) of SARS-CoV, MERS-CoV, and SARS-CoV-2 to be more flexible than the PBM of hCoVs 229E, NL63, OC43, and HKU1. We speculate that the increased flexibility of the PBM may provide the more virulent hCoVs with a greater degree of freedom, which can allow them to bind to different host proteins and can contribute to a more severe form of the disease. This is the first paper to predict the topologies and model 3D structures of all seven hCoVs E proteins, providing novel insights for possible drug and/or vaccine development.

Integrative approach for detecting membrane proteins

Background Membrane proteins are key gates that control various vital cellular functions. Membrane proteins are often detected using transmembrane topology prediction tools. While transmembrane topology prediction tools can detect integral membrane proteins, they do not address surface-bound proteins. In this study, we focused on finding the best techniques for distinguishing all types of membrane proteins. Results This research first demonstrates the shortcomings of merely using transmembrane topology prediction tools to detect all types of membrane proteins. Then, the performance of various feature extraction techniques in combination with different machine learning algorithms was explored. The experimental results obtained by cross-validation and independent testing suggest that applying an integrative approach that combines the results of transmembrane topology prediction and position-specific scoring matrix (Pse-PSSM) optimized evidence-theoretic k nearest neighbor (OET-KNN) predictors yields the best performance. Conclusion The integrative approach outperforms the state-of-the-art methods in terms of accuracy and MCC, where the accuracy reached a 92.51% in independent testing, compared to the 89.53% and 79.42% accuracies achieved by the state-of-the-art methods.

Designing an Outer Membrane Protein (Omp-W) Based Vaccine for Immunization against Vibrio and Salmonella: An in silico Approach

Background: Cholera triggered by Vibrio cholerae remains the main reason for morbidity and mortality all over the world. In addition, salmonellosis is regarded as an infectious disease that makes it essential for the identification and detection of Salmonella. With a beta-barrel structure consisting of eight non-parallel beta strands, OmpW family is widely distributed among gram-negative bacteria. Moreover, OmpW isolated from S. typhimurium and Vibrio cholerae can be used in vaccine design. Methods: Topology prediction was determined. T-cell and B-cell epitopes were selected from exposed areas, and sequence conservancy was evaluated. The remaining loops and inaccessible residues were removed to prepare OmpW-1. High antigenicity peptides were detected to replace inappropriate residues to obtain OmpW-2. Physicochemical properties were assessed, and antigenicity, hydrophobicity, flexibility, and accessibility were compared to the native Omp-W structure. Low score areas were removed from the designed structure for preparing the OmpW-3. To construct OmpW-4, TTFrC was used as T-CD4+ cell-stimulating factor and CTB as adjuvant to the end of the C-terminal of this sequence, which can increase the antigenicity and sequence density. The sequences were re-analyzed to delete the unfavorable residues. Besides, the solubility of the mature OmpW and the designed structure were predicted while overexpressed in E. coli. Results: The designed vaccine is a stable protein which has immune cells recognizing epitopes and is considered as an antigen. The construct can be overexpressed in a E. coli. Conclusion: The multi-epitope vaccine is a suitable stimulator for immune system and would be a candidate for experimental research. Recent patents describing numerous inventions related to the clinical facets of vaccine peptide against human infectious disease.