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The lack of effective medicines or vaccines, combined with climate change and other environmental factors, annually subjects a significant proportion of the world's inhabitants to the risk of dengue virus (DENV) infection. These conditions increase the likelihood of exposure to mosquito-borne diseases such as dengue fever. Hence, many research approaches tend to develop efficient vaccine candidates against the dengue virus. Therefore, we used immunoinformatics and bioinformatics to design a construction for developing a candidate vaccine against dengue virus serotypes. In this study, the in silico structure, containing the non-structural protein 1 region (NS1) (consensus and epitope), the envelope domain III protein (EDIII) as the structural part of the virus construction, and the bc-loop of envelope domain II (EDII) as the neutralizing and protected epitope, were employed. We utilized in silico tools to enhance the immunogenicity and effectiveness of dengue virus vaccine candidates. Evaluations included refining and validating physicochemical characteristics, B and T-cell epitopes, homology modeling, and the three-dimensional structure to assess the designed vaccine's quality. In silico results for tertiary structure prediction and validation revealed high-quality modeling for all vaccine constructs. Additionally, the instructed model demonstrated stability throughout molecular dynamics simulation. The results of the immune simulation suggested that the titers of IgG and IgM could be raised to desirable values following injection into in vivo models. It can be concluded that the designed construct effectively induce humoral and cellular immunity and can be proposed as effective vaccine candidate against four dengue serotypes.Communicated by Ramaswamy H. Sarma.

Since the onset of the global epidemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whole genome sequencing of virus in all countries has been considered to track and predict virus transmission and variation patterns. In the current study we reported a novel complete genome sequence of SARS-CoV-2 isolated from Iran. Genomics variations and protein sequences were evaluated for the isolated sequence and seven Iranian complete genome sequences of SARS-CoV-2 from NCBI using the reference genome of the SARS-CoV-2 Wuhan-Hu-1. The results showed six nucleotide substitutions. The multiple sequence alignment of the spike protein of the Wuhan-Hu-1 strain and the emerging variants indicated similar its residue pattern in the current sequence to the Wuhan-Hu-1 strain. There were relatively similar binding affinity and residues involved in the interactions of the spike receptor-binding domain (RBD) of the Wuhan-Hu-1 strain, the variants and Hormozgan With angiotensin-converting enzyme 2 (ACE2). Tracing the phylogeny of virus indicated distinct clustering of Iranian variants in branches close to the Asian countries. The mutation effect study on the function of proteins predicted neutral impact of all six nucleotide substitutions. However, the free energy calculations indicated a decreasing the protein stability related to the mutations. This data, consistent with similar studies, showed that despite the high similarity in the nucleotide sequence of the SARS-CoV-2, the mutation pattern varies from country to country. Therefore, any country can benefit from these studies to track and find appropriate strategies for treating and controlling the epidemic.Communicated by Ramaswamy H. Sarma.

Aberrant activation of Wnt/β-catenin signaling pathway, due to the genetic or epigenetic changes, is responsible for tumorigenesis in epithelial cells of different types of cancer such as colorectal cancer. Secreted Frizzled-Related Protein-1 (SFRP1), as one of the antagonist proteins of this pathway, is hyper-methylated in colorectal cancer leading to the formation of Wnt-Fz-LRP and activation of Wnt/β-catenin signaling pathway. We aimed to design antagonist peptides based on SFRP1 structure against wingless-type 2 (Wnt2), a highly expressed ligand in different cancers like colorectal cancer, to inhibit the formation of the initial triple complex of Wnt-Fz-LRP. After homology modeling of SFRP1, molecular docking showed that Wnt2 and SFRP1 interact in the same mode of xWnt8-mFz8 and hWnt3-mFz8 through the thumb and finger binding sites. These binding sites were selected for designing peptides using either substitution or deep learning-based approaches. The efficiency of each designed peptide in interacting with Wnt2 was evaluated by molecular docking. Stability assessment of Wnt2-peptide complexes via molecular dynamic (MD) revealed that the designed peptides could effectively interact with Wnt2 binding sites during the simulation. However, the designed peptides against the thumb site had higher binding affinity and hydrogen bonds compared to the initial sequence. The secondary structure of the designed peptides indicated an alpha-helix structure which is a favorable structure for peptide drugs. Computing the physicochemical properties of peptides predicted a fairly acceptable structure which made them promising candidates in the treatment of cancers like CRC.

The development of bacterial resistance toward antibiotics has been led to pay attention to the antimicrobial peptides (AMPs). The common mechanism of AMPs is disrupting the integrity of the bacterial membrane. One of the most accessible targets for α-defensins human neutrophil peptide-1 (HNP-1) is lipid II. In the present study, we performed homology modeling and geometrical validation of human neutrophil defensin 1. Then, the conformational and physicochemical properties of HNP-1 derived peptides 2Abz 14 S 29 , 2Abz 23 S 29 , and HNP1ΔC18A, as well as their interaction with lipid II were studied computationally. The overall quality of the predicted model of full protein was -5.14, where over 90% of residues were in the most favored and allowed regions in the Ramachandran plot. Although HNP-1 and HNP1ΔC18A were classified as unstable peptides, 2Abz 14 S 29 and 2Abz 23 S 29 were stable, based on the instability index values. Molecular docking showed similar interaction pattern of peptides and HNP-1 to lipid II. Molecular dynamic simulations revealed the overall stability of conformations, though the fluctuations of amino acids in the modified peptides were relatively higher than HNP-1. Further, the binding affinity constant (Kd) of HNP-1 and 2Abz 23 S 29 in complex with lipid II was 10 times stronger than 2Abz 14 S 29 and HNP1ΔC18A. Overall, computational studies of conformational and interaction patterns have signified how derived peptides could have displayed relatively similar antimicrobial results compared to HNP-1 in the reported experimental studies. Chemical modifications not only have improved the physicochemical properties of derived peptides compared to HNP-1, but also they have retained the similar pattern and binding affinity of peptides. Communicated by Ramaswamy H. Sarma.

Pertussis, caused by Bordetella pertussis is still one of the controversial diseases worldwide due to its high prevalence in both the developed and the developing countries, especially among young children. As currently approved vaccines are not protective enough and provide Th2-type immune responses, there is an urgent need to develop new vaccines. In the current study, we applied the C-terminal fragment of Clostridium perferingens enterotoxin (C-CPE) as a delivery system and F1S1 fragment (Filamentous hemagglutinin (F1) and subunit 1 of pertussis toxin (S1) of B. pertussis to design a novel chimeric protein in silico , to target Claudin-4 receptors in mice lung cells. To achieve this goal, the primary, secondary and tertiary structures of the fusion protein were evaluated and the interaction of this protein with Claudin-4 receptors was studied. Molecular dynamic (MD) simulation analysis was performed to investigate the physical movement of atoms in a fixed period. According to the results; the full-length fusion protein has consisted of 807 amino acid residues which could be classified as a stable protein. There was a convenient consistency between the 3D predicted structure and the secondary structure prediction. An acceptable percentage of the residues were also detected in the most favored and allowed regions for the model. Based on HADDOCK results, there were no considerable differences between the interactions and MD simulation analysis, indicating that the predicted structures were stable during the simulation. Altogether, the data reported in this study represents the first step toward developing a nasal vaccine candidate against B. pertussis infection. Communicated by Ramaswamy H. Sarma.