The 2019 novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has caused a large number of deaths, with thousands of confirmed cases worldwide. The present study followed computational approaches to identify Band T-cell epitopes for the spike (S) glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified 24 peptide stretches on the SARS-CoV-2 S protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface, of which 20 are surface exposed and predicted to have reasonable epitope binding efficiency. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics. Also, identified T-cell epitopes might be considered for incorporation in vaccine designs.

Alzheimer's disease (AD) is an irreversible memory disorder associated with multiple neuropathological events including amyloid aggregation that triggers oxidative stress and mitochondrial dysfunction in humans. Herein, a new artificial chaperone, benzimidazole functionalized polyfluorene (PFBZ) is reported to efficiently sequester toxic amyloid beta (Aβ) by binding at their 'amyloidogenic domain' (Aβ16−21) with unprecedented selectivity and prevent amyloid-mediated neuronal damage in a wild-type (WT) mouse model. An accurate dose of PFBZ chaperone successfully attenuated an amyloid triggered internal hemorrhage and pyknosis in the cerebral cortex of WT mice. The structural advantage of the polymer results in an efficient Cu(II) chelation arresting a redox cycle to prevent reactive oxygen species (ROS) generation and protect mitochondria from ROS mediated damage. This was further evidenced by caspase activation and mitochondrial membrane potential (MMP) biomarkers and was complemented by brain histology and electron microscopy data which revealed that the PFBZ chaperone provided a protective coating over the amyloid surface and resists from interacting with cell membrane and prevents inducing toxicity. This conjugated polymer artificial chaperone-based nanodrug showed exceptional properties such as its multipotent and highly biocompatible nature, the first of its kind with specific amyloid (Aβ16−21) targeting behavior, bioimaging, and BBB permeability with a potential to suppress amyloid triggered neurotoxicity implicated in numerous human disorders through a rare synergistic mechanism.

Small-molecule-based Cl − ion carriers are gaining revived attention because of their recently discovered role toward anticancer activity. Herein, we showed that the anticancer agents, PITENINs, have an efficient transmembrane Cl − ion transport activity. Theoretical calculations, 1 H NMR titration, and spectrophotometric analysis suggest that the PITENINs strongly bind with a Cl − ion. In addition to the lipophilicity, the presence of both acylthiourea and phenolic OH moieties of the compounds plays a crucial role in the transport of Cl − ions. Among the tested compounds, PIT-1 and DM-PIT-1 showed higher Cl − ion selectivity and transport efficiency. Mechanistic studies demonstrated that the potent compounds follow the H + /Cl − transport pathway. Cellular activity studies showed that the disruption of Cl − ion homeostasis by PIT-1 and DM-PIT-1 preferentially promotes apoptotic cell death.

24The 2019 novel severe respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak 25 has caused a large number of deaths with thousands of confirmed cases worldwide. The present 26 study followed computational approaches to identify B-and T-cell epitopes for spike 27 glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We 28 identified twenty-four peptide stretches on the SARS-CoV-2 spike protein that are well 29 conserved among the reported strains. The S protein structure further validated the presence of 30 predicted peptides on the surface. Out of which twenty are surface exposed and predicted to 31 have reasonable epitope binding efficiency. The work could be useful for understanding the 32 immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in 33 designing some peptide-based diagnostics. 34 35 36 37 38 39 40 41 42 43 44 45 46 47Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent 51 pandemic and declared as a public health emergency by World Health Organization (WHO) 1 . 52The disease rapidly spread across the globe and caused havoc to humanity 2 . By the end of 53 March, SARS-CoV-2 had spread to 200 countries and infected over 4,50,000 people 3 . The 54 WHO is continuously monitoring and updating the health-related plans to curtail the disease 55 spread. The absence of specific treatment and vaccine worsen the situation and threat the world. 56 International Committee on Taxonomy of Viruses (ICTV), classified SARS-CoV-2 57 under family coronaviridae of order nidovirales. The genomic sequence of SARS-CoV-2 58 isolated from the bronchoalveolar lavage fluid of a patient from the Wuhan, China showed a 59 length of 29,903 nucleotides (GenBank accession number NC_045512) 4 . The SARS-CoV-2 60 contains a positive single-stranded RNA with 5ˊ and 3ˊ UTR. The genome codes for ORF1a, 61 ORF1b, Spike (S), ORF3a, ORF3b, Envelope (E), Membrane (M), ORF6, ORF7a, ORF7b, 62ORF8, ORF9b, ORF14, Nucleocapsid (N), and ORF10 from 5ˊ to 3ˊ 4,5 . 63The S glycoprotein forms homotrimers and represents a potential target for therapeutic 64 and vaccine design as it mediates viral entry into host cells 6,7 . S glycoprotein comprises of two 65 functional subunits. Whereas the S1 subunit is responsible for binding to the host cell receptor, 66 the S2 subunit is responsible for the fusion of the viral with the cell membrane. Usually, in 67 CoVs, S is cleaved at the boundary between the S1 and S2 subunits, which remain non-68 covalently bound in the prefusion conformation, to activate the protein for membrane fusion 69 via extensive irreversible conformational changes [8][9][10] . Setting apart from other SARS-CoVs, it 70 is found that S glycoprotein of SARS-CoV-2 harbors a furin cleavage site at the boundary 71 between the S1/S2 subunits 11 . By now, it is evident that SARS-CoV-2 S uses angiotensin-72 converting enzyme 2 (ACE2) receptor-mediated entry into cells. It is found that the receptor-73 was not certified by peer review) is th...

Aim:This study was conducted to understand whether serum level of the steroid and metabolic hormones may be indicative of their level in ovarian follicular fluid (FF) in porcine, and its influence on fertility.Materials and Methods:Ovaries from pigs (n=32) of two genetic groups, namely, native (Ghungroo; n=16) and crossbred (Hampshire × Ghungroo; n=16) were collected. Both the genetic groups comprised gilts (n=8) and sows (n=8), and sows were in luteal phase of estrus cycle. FF was aspirated from small, medium and large follicles, and centrifuged for the collection of supernatant for further analysis. Blood samples were collected from the same animals, and serum was separated. Hormones, namely, cortisol, T3, T4 and testosterone were estimated by radioimmunoassay. Two-way ANOVA was used for analysis of data considering genetic background (native or crossbred), stage of reproductive life (gilt or sow), and source of sample (serum or FF) as fixed effects.Results:It was observed that all the hormones except cortisol differed significantly (p<0.01) based on genetic background. Stage of reproductive life and source of sample did not affect the studied hormonal level. Within the genetic groups, stage of reproductive life influenced T3 (p<0.01), cortisol (p<0.05) and testosterone (p<0.01) level in crossbred pigs as compared to T3 (p<0.01) only in native pigs. The level of T3 in serum, as well as FF, was higher (p<0.01) in Ghungroo gilts compared to sows. However, a reverse of this was observed in the case of crossbred pigs. The level of cortisol (p<0.05) and testosterone (p<0.01) was higher in crossbred sows than gilts in both serum and FF.Conclusion:The study revealed that serum level of the steroid and metabolic hormones is indicative of their level in the ovarian FF. Further, varying level of steroid and metabolic hormones in pigs based on genetic background may be due to variation in body size, rate of energy metabolism and stage of (re)productive life.