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Viral pathogenesis typically involves numerous molecular mechanisms. Protein aggregation is a relatively unknown characteristic of viruses, despite the fact that viral proteins have been shown to form terminally misfolded forms. Zika virus (ZIKV) is a neurotropic one with the potential to cause neurodegeneration. Its protein amyloid aggregation may link the neurodegenerative component to the pathogenicity associated with the viral infection. Therefore, we investigated protein aggregation in the ZIKV proteome as a putative pathogenic route and one of the alternate pathways. We discovered that it contains numerous anticipated aggregation‐prone regions in this investigation. To validate our prediction, we used a combination of supporting experimental techniques routinely used for morphological characterization and study of amyloid aggregates. Several ZIKV proteins and peptides, including the full‐length envelope protein, its domain III (EDIII) and fusion peptide, Pr N‐terminal peptide, NS1 β‐roll peptide, membrane‐embedded signal peptide 2K, and cytosolic region of NS4B protein, were shown to be highly aggregating in our study. Because our findings show that viral proteins can form amyloids in vitro, we need to do a thorough functional study of these anticipated APRs to understand better the role of amyloids in the pathophysiology of ZIKV infection. [ABSTRACT FROM AUTHOR]

4H-Chromene derivatives are promising anticancer compounds known to bind within the colchicine binding site of the tubulin protein. Among these, the 2-amino-4-phenyl-4H-benzo[h]chromene-3-carbonitrile-based 4H-chromenes scaffold is known to produce a significant impact on tubulin proteins. Other molecules with similar pharmacophores are also known for their colchicine binding site targeting abilities. However, tubulin is not a single protein; multiple isoforms have been reported, and some are comparatively more important under malignant conditions. Therefore, the research findings presented herein include a detailed understanding of the interaction pattern of the 2-amino-4-phenyl-4H-benzo[h]chromene-3-carbonitrile series for their colchicine binding ability against various tubulin isoforms proteins. We have established the current series anticancer potential and structural activity relationship. The series revealed promising anticancer potential, and MNC-1 was the best among all. However, a serious side effect of this scaffold is a major problem, as these derivatives indiscriminately bind to the tubulin of malignant and normal cells. However, the expression profile of tubulin isoforms was found to be different in normal and malignant cell types. Therefore, selective killing of the malignant cell seems possible by designing a 4H-chromenes derivative selective against particular tubulin isoforms. The insights provided herein clearly indicate the differences in the binding pattern of different 4H-chromenes derivatives against different tubulin isoforms. Therefore, with precise structural modification, these molecules' selective targeting against cancer cells seems quite possible. [ABSTRACT FROM AUTHOR]

The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge of the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in the SARS-CoV and SARS-CoV-2 proteomes. An initial analysis using a panel of sequence-based predictors suggested the presence of multiple aggregation-prone regions (APRs) in these proteomes and revealed a strong aggregation propensity in some SARS-CoV-2 proteins. We then studied the in vitro aggregation of predicted aggregation-prone SARS-CoV and SARS-CoV-2 proteins and protein regions, including the signal sequence peptide and fusion peptides 1 and 2 of the spike protein, a peptide from the NSP6 protein, and the ORF10 and NSP11 proteins. Our results show that these peptides and proteins can form amyloid aggregates. We used circular dichroism spectroscopy to reveal the presence of β-sheet rich cores in aggregates and X-ray diffraction and Raman spectroscopy to confirm the formation of amyloid structures. Furthermore, we demonstrated that SARS-CoV-2 NSP11 aggregates are toxic to mammalian cell cultures. These results motivate further studies about the possible role of aggregation of SARS proteins in protein misfolding diseases and other human conditions. Bhardwaj et al., have explored the proteomes of SARS-CoV and SARS-CoV-2, and have demonstrated the amyloid formation of viral proteins, in vitro, through diverse biophysical techniques. [ABSTRACT FROM AUTHOR]

Japanese encephalitis virus (JEV) is one of the major causes of viral encephalitis all around the globe. Approximately 3 billion people in endemic areas are at risk of Japanese encephalitis. To develop a wholistic understanding of the viral proteome, it is important to investigate both its ordered and disordered proteins. However, the functional and structural significance of disordered regions in the JEV proteome has not been systematically investigated as of yet. To fill this gap, we used here a set of bioinformatics tools to analyze the JEV proteome for the predisposition of its proteins for intrinsic disorder and for the presence of the disorder‐based binding regions (also known as molecular recognition features, MoRFs). We also analyzed all JEV proteins for the presence of the probable nucleic acid‐binding (DNA and RNA) sites. The results of these computational studies are experimentally validated using JEV capsid protein as an illustrative example. In agreement with bioinformatic analysis, we found that the N‐terminal region of the JEV capsid (residues 1–30) is intrinsically disordered. We showed that this region is characterized by the temperature response typical for highly disordered proteins. Furthermore, we have experimentally shown that this disordered N‐terminal domain of a capsid protein has a noticeable 'gain‐of‐structure' potential. In addition, using DOPS liposomes, we demonstrated the presence of pronounced membrane‐mediated conformational changes in the N‐terminal region of JEV capsid. In our view, this disorder‐centric analysis would be helpful for a better understanding of the JEV pathogenesis. [ABSTRACT FROM AUTHOR]

The ongoing life-threatening pandemic of coronavirus disease 2019 (COVID-19) has extensively affected the world. During this global health crisis, it is fundamentally crucial to find strategies to combat SARS-CoV-2. Despite several efforts in this direction and continuing clinical trials, no vaccine has been approved for it yet. To find a preventive measure, we have computationally designed a multi-epitopic subunit vaccine using immuno-informatic approaches. The structural proteins of SARS-CoV-2 involved in its survival and pathogenicity were used to predict antigenic epitopes. The antigenic epitopes were capable of eliciting a strong humoral as well as cell-mediated immune response, our predictions suggest. The final vaccine was constructed by joining the all epitopes with specific linkers and to enhance their stability and immunogenicity. The physicochemical property of the vaccine was assessed. The vaccine 3D structure prediction and validation were done and docked with the human TLR-3 receptor. Furthermore, molecular dynamics simulations of the vaccine-TLR-3 receptor complex are employed to assess its dynamic motions and binding stability in-silico. Based on this study, we strongly suggest synthesizing this vaccine, which further can be tested in-vitro and in-vivo to check its potency in a cure for COVID-19. [ABSTRACT FROM AUTHOR]