After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19.

Wnt signaling is one of the central mechanisms regulating tissue morphogenesis during embryogenesis and repair. The pivot of this signaling cascade is the Wnt ligand, which binds to receptors belonging to the Frizzled family or the ROR1/ROR2 and RYK family. This interaction governs the downstream signaling cascade (canonical/non-canonical), ultimately extending its effect on the cellular cytoskeleton, transcriptional control of proliferation and differentiation, and organelle dynamics. Anomalous Wnt signaling has been associated with several cancers, the most prominent ones being colorectal, breast, lung, oral, cervical, and hematopoietic malignancies. It extends its effect on tumorigenesis by modulating the tumor microenvironment via fine crosstalk between transformed cells and infiltrating immune cells, such as leukocytes. This review is an attempt to highlight the latest developments in the understanding of Wnt signaling in the context of tumors and their microenvironment. A dynamic process known as immunoediting governs the fate of tumor progression based on the correlation of various signaling pathways in the tumor microenvironment and immune cells. Cancer cells also undergo a series of mutations in the tumor suppressor gene, which favors tumorigenesis. Wnt signaling, and its crosstalk with various immune cells, has both negative as well as positive effects on tumor progression. On one hand, it helps in the maintenance and renewal of the leucocytes. On the other hand, it promotes immune tolerance, limiting the antitumor response. Wnt signaling also plays a role in epithelial-mesenchymal transition (EMT), thereby promoting the maintenance of Cancer Stem Cells (CSCs). Furthermore, we have summarized the ongoing strategies used to target aberrant Wnt signaling as a novel therapeutic intervention to combat various cancers and their limitations.

Zika virus (ZikV) has emerged as a potential threat to human health worldwide. A member of the Flaviviridae, ZikV is transmitted to humans by mosquitoes. It is related to other pathogenic vector-borne flaviviruses including dengue, West Nile and Japanese encephalitis viruses, but produces a comparatively mild disease in humans. As a result of its epidemic outbreak and the lack of potential medication, there is a need for improved vaccine/drugs. Computational techniques will provide further information about this virus. Comparative analysis of ZikV genomes should lead to the identification of the core characteristics that define a virus family, as well as its unique properties, while phylogenetic analysis will show the evolutionary relationships and provide clues about the protein's ancestry. Envelope glycoprotein of ZikV was obtained from a protein database and the most immunogenic epitope for T cells and B cells involved in cell-mediated immunity, whereas B cells are primarily responsible for humoral immunity. We mainly focused on MHC class I potential peptides. YRIMLSVHG, VLIFLSTAV and MMLELDPPF, GLDFSDLYY are the most potent peptides predicted as epitopes for CD4 and CD8 T cells, respectively, whereas MMLELDPPF and GLDFSDLYY had the highest pMHC-I immunogenicity score and these are further tested for interaction against the HLA molecules, using in silico docking techniques to verify the binding cleft epitope. However, this is an introductory approach to design an epitope-based peptide vaccine against ZikV; we hope that this model will be helpful in designing and predicting novel vaccine candidates.

Scaffold/matrix attachment regions (S/MARs) are DNA elements that serve to compartmentalize the chromatin into structural and functional domains. These elements are involved in control of gene expression which governs the phenotype and also plays role in disease biology. Therefore, genome-wide understanding of these elements holds great therapeutic promise. Several attempts have been made toward identification of S/MARs in genomes of various organisms including human. However, a comprehensive genome-wide map of human S/MARs is yet not available. Toward this objective, ChIP-Seq data of 14 S/MAR binding proteins were analyzed and the binding site coordinates of these proteins were used to prepare a non-redundant S/MAR dataset of human genome. Along with co-ordinate (location) details of S/MARs, the dataset also revealed details of S/MAR features, namely, length, inter-SMAR length (the chromatin loop size), nucleotide repeats, motif abundance, chromosomal distribution and genomic context. S/MARs identified in present study and their subsequent analysis also suggests that these elements act as hotspots for integration of retroviruses. Therefore, these data will help toward better understanding of genome functioning and designing effective anti-viral therapeutics. In order to facilitate user friendly browsing and retrieval of the data obtained in present study, a web interface, MARome (http://bioinfo.net.in/MARome), has been developed.

Reduced expression of Scaffold/Matrix Attachment Region Binding Protein 1 (SMAR1) is associated with various cancers resulting in poor prognosis of the diseases. However, the precise underlying mechanism elucidating the loss of SMAR1 requires ongoing study. Here, we show that SMAR1 is highly downregulated during aberrant Wnt3a signaling due to proteasomal degradation and predicted poor prognosis of colorectal cancer. However, substitution mutation (Arginine and Lysine to Alanine) in the D-box elements of SMAR1 viz. “RCHL” and “RQRL” completely abrogated its proteasomal degradation despite Wnt3a activity. SMAR1 inhibited Wnt/β-catenin signaling by recruiting Histone deacetylase-5 to β-catenin promoter resulting in reduced cell migration and invasion. Consequently, reduced tumor sizes in in-vivo NOD-SCID mice were observed that strongly associated with suppression of β-catenin. However, loss of SMAR1 led to enriched H3K9 Acetylation in the β-catenin promoter that further increased Wnt/β-catenin signaling activities and enhanced colorectal cancer progression drastically. Using docking and isothermal titration calorimetric studies we show that small microbial peptides viz. AT-01C and AT-01D derived from Mycobacterium tuberculosis mask the D-box elements of SMAR1. These peptides stabilized SMAR1 expression that further inhibited metastatic SW480 colorectal cancer cell migration and invasion. Drastically reduced subcutaneous tumors were observed in in-vivo NOD-SCID mice upon administration of these peptides (25 mg/kg body weight) intraperitoneally. Taken together our structural studies, in-vitro and in-vivo results strongly suggest that the D-box elements of SMAR1 represent novel druggable targets, where the microbial peptides hold promise as novel colorectal cancer therapeutics.

Obesity is one of the biggest public health concerns identified by an increase in adipose tissue mass as a result of adipocyte hypertrophy and hyperplasia. Pertaining to the importance of adipose tissue in various biological processes, any alteration in its function results in impaired metabolic health. In this review, we discuss how adipose tissue maintains the metabolic health through secretion of various adipokines and inflammatory mediators and how its dysfunction leads to the development of severe metabolic disorders and influences cancer progression. Impairment in the adipocyte function occurs due to individuals’ genetics and/or environmental factor(s) that largely affect the epigenetic profile leading to altered gene expression and onset of obesity in adults. Moreover, several crucial aspects of adipose biology, including the regulation of different transcription factors, are controlled by epigenetic events. Therefore, understanding the intricacies of adipogenesis is crucial for recognizing its relevance in underlying disease conditions and identifying the therapeutic interventions for obesity and metabolic syndrome.

Inhibition of fibrillation process and disaggregation of mature fibrils using small peptide are the promising remedial strategies to combat neurodegenerative diseases. However, designing peptide-based drugs to target β-sheet-rich amyloid has been a major challenge. The current work describes, for the first time, the amyloid inhibitory potential of the two short peptides (selected on the basis of predisposition of their amino acid residues toward β-sheet formation) using combination of biophysical, imaging methods, and docking approaches. Results showed that peptides employed different mechanisms to inhibit the amyloid fibrillation. Furthermore, they were also effective in blocking the amyloid fibrillation pathway. In contrary to the insulin fibrillar mesh, significantly less fibrillar species appeared in the presence of peptides, as confirmed by transmission electron microscopy. Circular dichroism analysis indicated that although peptides did not stabilize the native state of insulin, they inhibited amyloid aggregation by reducing the formation of β-sheet rich structures. Hemolytic assay revealed the non-hemolytic nature of the species formed when insulin was co-incubated with the peptides. Therefore, despite the inherent potential to form β-sheet structure, these peptides inhibited the amyloid formation and potentially can be used as therapeutics for the treatment of amyloid-related diseases.

It is an essential for any antibacterial agent (for clinical application), that it should have a high and selective toxicity towards the bacterial cells only, and should not affect the human cells at the concentration used. Graphene quantum dots (GQDs) have emerged as a potential candidate for biomedical applications. However, a simple, low cost, safe, easy to execute, one-step synthesis of uniform, and monodispersed GQDs with selective toxicity towards the bacterial cells rather than the mammalian cells, is difficult to achieve. Here, we have reported a one-step, low-cost, aqueous-phase, simple approach for the complete conversion of multiwalled carbon nanotubes into the water-dispersible GQDs with an average size ~3 nm using sodium bismuthate (NaBiO 3 ) as a strong oxidant. The cyclic voltammetry and X-ray photoelectron spectroscopy results indicated that the as-synthesized GQDs suspension possess almost negligible amount of metallic impurities. The cytotoxicity studies of GQDs against mammalian NIH 3T3 (mouse embryo fibroblast cells) and HEK 293T (human embryonic kidney cells) cells showed that the as-synthesized GQDs were non-cytotoxic up to the concentration of ~200 µg mL -1 . The antimicrobial study shows that the synthesized GQDs have high and selective toxicity towards the bacterial cells with minimum inhibitory concentration of as-synthesized GQDs as ~256 µg mL -1 for E. coli and B. subtilis, and ~512 µg mL -1 for P. aeruginosa and S. aureus. The scanning electron microscopy and atomic force microscopy images show the extensive cell damage via the perturbation of bacterial cell walls, which was consistent with the enhancement of reactive oxygen species production by almost two times in the bacterial cells upon incubation with ~256 µg mL -1 of GQDs. Our study suggested that the as-synthesized GQDs can be used as a potential candidate for clinical applications as they possess high toxicity to bacterial cells and low toxicity to mammalian cells.It can be noticed from the figure 2b that for both, the MWCNTs as well as the GQDs, the G-peak splits in two sub-bands, second harmonic G-band and tangential G-band. This splitting is due to the strain induced from curvature and confinement, respectively. The second harmonic G-band peaks for MWCNTs and GQDs were observed at 1605 cm -1 and 1621 cm -1 , respectively. The tangential G-band for MWCNTs and GQDs appeared as a shoulder at 1575 cm -1 and 1582 cm -1 , respectively (Table S1). The gradual shift in the G-band denotes greater lattice and structural disorder in GQDs. 24 Chemical analysis of as-synthesized GQDsThe X-ray photoelectron spectroscopy (XPS) analysis was also performed to determine chemical composition of the as-synthesized GQDs. The XPS survey scan shows the presence of carbon, oxygen, and nitrogen peaks in the GQDs sample ( Figure S5). The absence of bismuth or any other metal ion peak in the 12 h treated GQDs shows that the as-synthesized GQDs were free from the oxidants used to break it down. The presence of nitrogen was found in the XPS spectra bec...