Using In Silico Bioinformatics Algorithms for the Accurate Prediction of the Impact of Spike Protein Mutations on the Pathogenicity, Stability, and Functionality of the SARS-CoV-2 Virus and Analysis of Potential Therapeutic Targets.

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have used bioinformatics to investigate seventeen mutations in the spike protein of SARS-CoV-2, as this mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapies. Two mutations, H146Y and S221W, were identified as being most pathogenic. Mutations at positions D614G, A829T, and P1263L might also have deleterious effects on protein function. We hypothesized that candidate small molecules may be repurposed to combat viral infection. We investigated changes in binding energies of the ligands and the mutant proteins by assessing molecular docking. For an understanding of cellular function and organization, protein-protein interactions are also critical. Protein-protein docking for naïve and mutated structures of SARS-CoV-2 S protein was evaluated for their binding energy with the angiotensin-converting enzyme 2 (ACE2). These interactions might limit the binding of the SARS-CoV-2 spike protein to the ACE2 receptor or may have a deleterious effect on protein function that may limit infection. These results may have important implications for the transmission of SARS-CoV-2, its pathogenesis, and the potential for drug repurposing and immune therapies.

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment.

Hypoxia is a common feature of solid tumors, and develops because of the rapid growth of the tumor that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. It has been reported that tumor hypoxia can: activate angiogenesis, thereby enhancing invasiveness and risk of metastasis; increase survival of tumor, as well as suppress anti-tumor immunity and hamper the therapeutic response. Hypoxia mediates these effects by several potential mechanisms: altering gene expression, the activation of oncogenes, inactivation of suppressor genes, reducing genomic stability and clonal selection. We have reviewed the effects of hypoxia on tumor biology and the possible strategiesto manage the hypoxic tumor microenvironment (TME), highlighting the potential use of cancer stem cells in tumor treatment.

The role of microRNAs involved in the disorder of blood-brain barrier in the pathogenesis of multiple sclerosis.

miRNAs are involved in various vital processes, including cell growth, development, apoptosis, cellular differentiation, and pathological cellular activities. Circulating miRNAs can be detected in various body fluids including serum, plasma, saliva, and urine. It is worth mentioning that miRNAs remain stable in the circulation in biological fluids and are released from membrane-bound vesicles called exosomes, which protect them from RNase activity. It has been shown that miRNAs regulate blood-brain barrier integrity by targeting both tight junction and adherens junction molecules and can also influence the expression of inflammatory cytokines. Some recent studies have examined the impact of certain commonly used drugs in Multiple Sclerosis on miRNA levels. In this review, we will focus on the recent findings on the role of miRNAs in multiple sclerosis, including their role in the cause of MS and molecular mechanisms of the disease, utilizing miRNAs as diagnostic and clinical biomarkers, using miRNAs as a therapeutic modality or target for Multiple Sclerosis and drug responses in patients, elucidating their importance as prognosticators of disease progression, and highlighting their potential as a future treatment for MS.

Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking.

SARS-CoV-2 (COVID-19) is the causative organism for a pandemic disease with a high rate of infectivity and mortality. In this study, we aimed to assess the affinity between several available small molecule and proteins, including Abl kinase inhibitors, Janus kinase inhibitor, dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papain-like protease inhibitors, using binding simulation, to test whether they may be effective in inhibiting COVID-19 infection through several mechanisms. The efficiency of inhibitors was evaluated based on docking scores using AutoDock Vina software. Strong ligand-protein interactions were predicted among some of these drugs, that included: Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control as potential inhibitors or lead compounds against the SARS-CoV-2. It is also worth highlighting the powerful immunomodulatory role of other drugs, such as Abivertinib that inhibits pro-inflammatory cytokine production associated with cytokine release syndrome (CRS) and the progression of COVID-19 infection. The potential role of other Abl kinase inhibitors, including Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS), indicate that this drug may be useful for COVID-19, as the SARS-CoV-2 genome is similar to SARS-CoV.

Antibacterial Assessment of Zinc Sulfide Nanoparticles against Streptococcus pyogenes and Acinetobacter baumannii.

BACKGROUND: Due to the appearance of resistant bacterial strains against the antimicrobial drugs and the reduced efficiency of these valuable resources, the health of a community and the economies of countries have been threatened. OBJECTIVE: In this study, the antibacterial assessment of zinc sulfide nanoparticles (ZnS NPs) against Streptococcus pyogenes and Acinetobacter baumannii has been performed. METHODS: ZnS NPs were synthesized through a co-precipitation method using polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and polyethylene glycol (PEG-4000). The size and morphology of the synthesized ZnS NPs were determined by a scanning electron microscope (SEM) and it was found that the average size of the applied NPs was about 70 nm. In order to evaluate the antibacterial effect of the synthesized ZnS NPs, various concentrations (50µg/mL, 100 µg/mL and 150 µg/mL) of ZnS NPs were prepared. Antibacterial assessments were performed through the disc diffusion method in Mueller Hinton Agar (MHA) culture medium and also the optical density (OD) method was performed by a UV-Vis spectrophotometer in Trypticase™ Soy Broth (TSB) medium. Then, in order to compare the antibacterial effects of the applied NPs, several commercial antibiotics including penicillin, amikacin, ceftazidime and primaxin were used. RESULTS: The achieved results indicated that the antibacterial effects of ZnS NPs had a direct relation along with the concentrations and the concentration of 150 µg/mL showed the highest antibacterial effect in comparison with others. In addition, the ZnS NPs were more effective on Acinetobacter baumannii. CONCLUSION: The findings of this research suggest a novel approach against antibiotic resistance.