3CL hydrolase-based multiepitope peptide vaccine against SARS-CoV-2 using immunoinformatics

The present study provides the first multiepitope vaccine construct using the 3CL hydrolase protein of SARS-CoV-2. The coronavirus 3CL hydrolase (Mpro) enzyme is essential for proteolytic maturation of the virus. This study was based on immunoinformatics and structural vaccinology strategies. The design of the multiepitope vaccine was built using helper T-cell and cytotoxic T-cell epitopes from the 3CL hydrolase protein along with an adjuvant to enhance immune response; these are joined to each other by short peptide linkers. The vaccine also carries potential B-cell linear epitope regions, B-cell discontinuous epitopes, and interferon-γ-inducing epitopes. Epitopes of the constructed multiepitope vaccine were found to be antigenic, nonallergic, nontoxic, and covering large human populations worldwide. The vaccine construct was modeled, validated, and refined by different programs to achieve a high-quality three-dimensional structure. The resulting high-quality model was applied for conformational B-cell epitope selection and docking analyses with toll-like receptor-3 for understanding the capability of the vaccine to elicit an immune response. In silico cloning and codon adaptation were also performed with the pET-19b plasmid vector. The designed multiepitope peptide vaccine may prompt the development of a vaccine to control SARS-CoV-2 infection.     

In utero immune programming of autism spectrum disorder (ASD)

Maladaptation of immune tolerance at the maternal-fetal interface affects balanced maternal-fetal cross-talk and placental health and is associated with adverse pregnancy outcomes. The concept of in utero programming of childhood and adulthood diseases has revolutionized the research on the role of pregnancy in maternal, neonatal, and adult health. However, it is not yet well understood whether dysregulation of uterine immunity contributes to any health consequences during childhood or later in life. Recent observations in mice and humans have strongly supported the notion that uterine immunity during pregnancy determines the health trajectory of the offspring and significantly impacts cognitive function and mental health. Importantly, IL-17a producing Th17 T cells have been projected as the main contributors to heterogeneous pathological and behavioral phenotypes associated with autism spectrum disorder (ASD). However, since normal pregnancy is associated with little or no Th17 cells at the maternal-fetal interface, it is not clear how and when the Th17 T cells are generated and which interventions can ameliorate the ASD-like features in newborns. We propose that infection-associated uterine immune activation within a critical window of development may propel trans-differentiation of Th17 T cells that eventually affect fetal brain development and induce ASD-like behavioral phenotype in the offspring.     

Assessment of the Antiulcer Potential of Moringa oleifera Root-Bark Extract in Rats

In the present study, an ethanolic root-bark extract of Moringa oleifera (MO) was examined for its antiulcer potential in albino Wistar rats using two experimental models: ethanol-induced and pylorus ligation-induced gastric ulceration. The extract was orally administered at three different doses (150, 350, and 500 mg/kg) for 15 consecutive days. The antiulcer effects in rats treated with different doses of the extract and omeprazole (30 mg/kg, p.o.) were determined and compared statistically with the antiulcer effects in the control rats treated with saline (NaCl, 0.9%). The MO at doses of 350 and 500 mg/kg decreased the ulcer index significantly as compared to the control group (p < 0.01). The percentage protections against gastric ulcers were 82.58%, 85.13%, and 86.15% for MO doses of 150, 350, and 500 mg/kg, respectively, in the pylorus-ligated ulcer model and 55.75%, 59.33%, and 78.51%, respectively, in the ethanol-induced ulcer model. The MO significantly reduced the free acidity, total acidity, and ulcer index (p < 0.01) and increased the pH of gastric content compared with the control group. This study suggests that MO possesses valuable antiulcer, antisecretory, and cytoprotective activity. Thus, an ethanolic root-bark extract of Moringa oleifera can be used as source for an antiulcer drug.