Fabrication and characterization of an antibacterial chitosan/silk fibroin electrospun nanofiber loaded with a cationic peptide for wound-dressing application.

Wound infections are still problematic in many cases and demand new alternatives for current treatment strategies. In recent years, biomaterials-based wound dressings have received much attention due to their potentials and many studies have been performed based on them. Accordingly, in this study, we fabricated and optimized an antibacterial chitosan/silk fibroin (CS/SF) electrospun nanofiber bilayer containing different concentrations of a cationic antimicrobial peptide (AMP) for wound dressing applications. The fabricated CS/SF nanofiber was fully characterized and compared to the electrospun silk fibroin and electrospun chitosan alone in vitro. Then, the release rate of different concentrations of peptide (16, 32, and 64 µg/ml) from peptide-loaded CS/SF nanofiber was investigated. Finally, based on cytotoxic activity, the antibacterial activity of scaffolds containing 16 and 32 µg/ml of the peptide was evaluated against standard and multi-drug resistant strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa isolated from burn patients. The peptide-loaded CS/SF nanofiber displayed appropriate mechanical properties, high water uptake, suitable biodegradation rate, a controlled release without cytotoxicity on Hu02 human foreskin fibroblast cells at the 16 and 32 µg/ml concentrations of peptide. The optimized CS/SF containing 32 µg/ml peptide showed strong antibacterial activity against all experimental strains from standard to resistance. The results showed that the fabricated antimicrobial nanofiber has the potential to be applied as a wound dressing for infected wound healing, although further studies are needed in vivo.

Structure-based study of immune receptors as eligible binding targets of coronavirus SARS-CoV-2 spike protein.

One of the most important challenges in the battle against contagious SARS-CoV-2 is subtle identification of the virus pathogenesis. The broad range of COVID-19 clinical manifestations may indicate diversity of virus-host cells. Amongst key manifestations, especially in severe COVID-19 patients, reduction and/or exhaustion of lymphocytes, monocytes, basophils, and dendritic cells are seen.; therefore, it is required to recognize that how the virus infects the cells. Interestingly, angiotensin-converting enzyme 2 (ACE2) as the well-known receptor of SARS-CoV-2 is low or non-expressed in these cells. Using computational approach, several receptor candidates including leukocyte surface molecules and chemokine receptors that expressed in most lineages of immune cells were evaluated as the feasible receptor of spike receptor-binding domain (RBD) of SARS-CoV-2. The results revealed the higher binding affinity of CD26, CD2, CD56, CD7, CCR9, CD150, CD4, CD50, XCR1 and CD106 compared to ACE2. However, the modes of binding and amino acids involved in the interactions with the RBD domain of spike were various. Overall, the affinity of immune receptor candidates in binding to SARS-CoV-2 RBD may offer insight into the recognition of novel therapeutic targets in association with COVID-19.

The Anti-Proliferative Effect of a Newly-Produced Anti-PSCA-Peptide Antibody by Multiple Bioinformatics Tools, on Prostate Cancer Cells.

BACKGROUND: Prostate Stem Cell Antigen (PSCA) is a small cell surface protein, overexpressed in 90% of prostate cancers. Determination of epitopes that elicit an appropriate response to the antibody generation is vital for diagnostic and immunotherapeutic purposes for prostate cancer treatment. Presently, bioinformatics B-cell prediction tools can predict the location of epitopes, which is uncomplicated, faster, and more cost-effective than experimental methods. OBJECTIVE: We aimed to predict a novel linear peptide for Prostate Stem Cell Antigen (PSCA) protein in order to generate anti-PSCA-peptide (p) antibody and to investigate its effect on prostate cancer cells. METHODS: In the current study, a novel linear peptide for PSCA was predicted using in silico methods that utilize a set of linear B-cell epitope prediction tools. Polyclonal antibody (anti-PSCA-p antibody "Patent No. 99318") against PSCA peptide was generated. The antibody reactivity was determined by the Enzyme-Linked Immunosorbent Assay (ELISA) and its specificity by immunocytochemistry (ICC), immunohistochemistry (IHC), and Western Blotting (WB) assays. The effect of the anti-PSCA-p antibody on PSCA-expressing prostate cancer cell line was assessed by Methylthiazolyldiphenyl- Tetrazolium bromide (MTT) assay. RESULTS: New peptide-fragment of PSCA sequence as "N-CVDDSQDYYVGKKN-C" (PSCA-p) was selected and synthesized. The anti-PSCA-p antibody against the PSCA-p showed immunoreactivity with PSCA-p specifically bound to PC-3 cells. Also, the anti-PSCA-p antibody strongly stained the prostate cancer tissues as compared to Benign Prostatic Hyperplasia (BPH) and normal tissues (P < 0.001). As the degree of malignancy increased, the staining intensity was also elevated in prostate cancer tissue (P < 0.001). Interestingly, the anti-PSCA-p antibody showed anti-proliferative effects on PC-3 cells (31%) with no growth inhibition effect on PSCA-negative cells. CONCLUSION: In this study, we developed a new peptide sequence (PSCA-p) of PSCA. The PSCA-p targeting by anti-PSCA-p antibody inhibited the proliferation of prostate cancer cells, suggesting the potential of PSCA-p immunotherapy for future prostate cancer studies.

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they are not specific and targeted. Therefore, several drugs have been investigated for their efficacy and safety in the treatment of COVID-19; most of them are undergoing clinical trials. This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial.

Computational Design of a Novel VLP-Based Vaccine for Hepatitis B Virus.

Hepatitis B virus (HBV) is a global virus responsible for a universal disease burden for millions of people. Various vaccination strategies have been developed using viral vector, nucleic acid, protein, peptide, and virus-like particles (VLPs) to stimulate favorable immune responses against HBV. Given the pivotal role of specific immune responses of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in infection control, we designed a VLP-based vaccine by placing the antibody-binding fragments of HBsAg in the major immunodominant region (MIR) epitope of HBcAg to stimulate multilateral immunity. A computational approach was employed to predict and evaluate the conservation, antigenicity, allergenicity, and immunogenicity of the construct. Modeling and molecular dynamics (MD) demonstrated the folding stability of HBcAg as a carrier in inserting Myrcludex and "a" determinant of HBsAg. Regions 1-50 and 118-150 of HBsAg were considered to have the highest stability to be involved in the designed vaccine. Molecular docking revealed appropriate interactions between the B cell epitope of the designed vaccine and the antibodies. Totally, the final construct was promising for inducing humoral and cellular responses against HBV.