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In the worrisome scenarios of various waves of SARS-CoV-2 pandemic, a comprehensive bioinformatics pipeline is essential to analyse the virus genomes in order to understand its evolution, thereby identifying mutations as signature SNPs, conserved regions and subsequently to design epitope based synthetic vaccine. We have thus performed multiple sequence alignment of 4996 Indian SARS-CoV-2 genomes as a case study using MAFFT followed by phylogenetic analysis using Nextstrain to identify virus clades. Furthermore, based on the entropy of each genomic coordinate of the aligned sequences, conserved regions are identified. After refinement of the conserved regions, based on its length, one conserved region is identified for which the primers and probes are reported for virus detection. The refined conserved regions are also used to identify T-cell and B-cell epitopes along with their immunogenic and antigenic scores. Such scores are used for selecting the most immunogenic and antigenic epitopes. By executing this pipeline, 40 unique signature SNPs are identified resulting in 23 non-synonymous signature SNPs which provide 28 amino acid changes in protein. On the other hand, 12 conserved regions are selected based on refinement criteria out of which one is selected as the potential target for virus detection. Additionally, 22 MHC-I and 21 MHC-II restricted T-cell epitopes with 10 unique HLA alleles each and 17 B-cell epitopes are obtained for 12 conserved regions. All the results are validated both quantitatively and qualitatively which show that from genetic variability to synthetic vaccine design, the proposed pipeline can be used effectively to combat SARS-CoV-2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Bisphenol A (BPA) is an endocrine disrupting chemical which poses great concern because of its high proportionate industrial production, omnipresent human exposure and budding toxic consequences in human. A plethora of previous studies has connected BPA to a variety of negative health outcomes and diabetes mellitus is among the first bencher. However, there is disagreement over the degree of toxic effects generated by low and high doses of BPA and critical period of exposure. Furthermore, the safe level of BPA determined by classical toxicological studies does not protect pancreatic islet cells from low dose effects of BPA. Thus, the extremities of toxic effects on pancreatic islets associated with BPA exposure are complicated and contentious. In this review, we highlighted different cellular and molecular pathways targeted by BPA to mediate its action on pancreatic islets with consideration of both low and high dose effects. Besides estrogen receptor α and β, BPA also uses non canonical membrane bound estrogen receptor and G-protein coupled estrogen receptor to confer its toxic effects. In doing so, BPA modulates ion channels, and transcription factors; causes aggregation of human islet amyloid polypeptide, endoplasmic reticulum and mitochondrial stress; and results in activation of NFκB in pancreatic β cells. BPA also renders a major shift in β to α cell ratio in islets causing deregulated glucagon secretion. Hence, understanding of various mechanisms of BPA action on the pancreatic islets will provide meaningful insights in recognizing the risk posed by exposure to low and high doses of BPA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Since the inception of SARS-CoV-2 in December 2019, many variants have emerged over time. Some of these variants have resulted in transmissibility changes of the virus and may also have impact on diagnosis, therapeutics and even vaccines, thereby raising particular concerns in the scientific community. The variants which have mutations in Spike glycoprotein are the primary focus as it is the main target for neutralising antibodies. SARS-CoV-2 is known to infect human through Spike glycoprotein and uses receptor-binding domain (RBD) to bind to the ACE2 receptor in human. Thus, it is of utmost importance to study these variants and their corresponding mutations. Such 12 different important variants identified so far are B.1.1.7 (Alpha), B.1.351 (Beta), B.1.525 (Eta), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota), B.1.617.1 (Kappa), B.1.617.2 (Delta), C.37 (Lambda), P.1 (Gamma), P.2 (Zeta), P.3 (Theta) and the recently discovered B.1.1.529 (Omicron). These variants have 84 unique mutations in Spike glycoprotein. To analyse such mutations, multiple sequence alignment of 77681 SARS-CoV-2 genomes of 98 countries over the period from January 2020 to July 2021 is performed followed by phylogenetic analysis. Also, characteristics of new emerging variants are elaborately discussed. The individual evolution of these mutation points and the respective variants are visualised and their characteristics are also reported. Moreover, to judge the characteristics of the non-synonymous mutation points (substitutions), their biological functions are evaluated by PolyPhen-2 while protein structural stability is evaluated using I-Mutant 2.0., (Copyright © 2022. Published by Elsevier B.V.)

The pandemic of COVID-19 has been haunting us for almost the past two years. Although, the vaccination drive is in full swing throughout the world, different mutations of the SARS-CoV-2 virus are making it very difficult to put an end to the pandemic. The second wave in India, one of the worst sufferers of this pandemic, can be mainly attributed to the Delta variant i.e. B.1.617.2. Thus, it is very important to analyse and understand the mutational trajectory of SARS-CoV-2 through the study of the 26 virus proteins. In this regard, more than 17,000 protein sequences of Indian SARS-CoV-2 genomes are analysed using entropy-based approach in order to find the monthly mutational trajectory. Furthermore, Hellinger distance is also used to show the difference of the mutation events between the consecutive months for each of the 26 SARS-CoV-2 protein. The results show that the mutation rates and the mutation events of the viral proteins though changing in the initial months, start stabilizing later on for mainly the four structural proteins while the non-structural proteins mostly exhibit a more constant trend. As a consequence, it can be inferred that the evolution of the new mutative configurations will eventually reduce., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The surge of SARS-CoV-2 has created a wave of pandemic around the globe due to its high transmission rate. To contain this virus, researchers are working around the clock for a solution in the form of vaccine. Due to the impact of this pandemic, the economy and healthcare have immensely suffered around the globe. Thus, an efficient vaccine design is the need of the hour. Moreover, to have a generalised vaccine for heterogeneous human population, the virus genomes from different countries should be considered. Thus, in this work, we have performed genome-wide analysis of 10,664 SARS-CoV-2 genomes of 73 countries around the globe in order to identify the potential conserved regions for the development of peptide based synthetic vaccine viz. epitopes with high immunogenic and antigenic scores. In this regard, multiple sequence alignment technique viz. Clustal Omega is used to align the 10,664 SARS-CoV-2 virus genomes. Thereafter, entropy is computed for each genomic coordinate of the aligned genomes. The entropy values are then used to find the conserved regions. These conserved regions are refined based on the criteria that their lengths should be greater than or equal to 60 nt and their corresponding protein sequences are without any stop codons. Furthermore, Nucleotide BLAST is used to verify the specificity of the conserved regions. As a result, we have obtained 17 conserved regions that belong to NSP3, NSP4, NSP6, NSP8, RdRp, Helicase, endoRNAse, 2'-O-RMT, Spike glycoprotein, ORF3a protein, Membrane glycoprotein and Nucleocapsid protein. Finally, these conserved regions are used to identify the T-cell and B-cell epitopes with their corresponding immunogenic and antigenic scores. Based on these scores, the most immunogenic and antigenic epitopes are then selected for each of these 17 conserved regions. Hence, we have obtained 30 MHC-I and 24 MHC-II restricted T-cell epitopes with 14 and 13 unique HLA alleles and 21 B-cell epitopes for the 17 conserved regions. Moreover, for validating the relevance of these epitopes, the binding conformation of the MHC-I and MHC-II restricted T-cell epitopes are shown with respect to HLA alleles. Also, the physico-chemical properties of the epitopes are reported along with Ramchandran plots and Z-Scores and the population coverage is shown as well. Overall, the analysis shows that the identified epitopes can be considered as potential candidates for vaccine design., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We investigated the combined effect of chitosan (CHT) and putrescine (PUT) on the postharvest shelf life of Capsicum fruit concerning the metabolism of reactive oxygen species (ROS) through direct and indirect effects on ripening characters cell wall hydrolyzing enzyme and ROS metabolism. The PUT and CHT directly affected quality indices like color, firmness and water loss with a concomitant oxidative bust in the development of O 2 •- and H 2 O 2 in fruit pulp. This was accompanied by significant suppression of respiratory flux, a decrease of total soluble solids and ascorbic acid content throughout postharvest storage. PUT applied with CHT modified the oxidative metabolism of fruits by a significant reduction in the level of O 2 •- and H 2 O 2 content. In addition, a significant accumulation of total polyamine under respective treatment was reasonably correlated with both ROS producing enzyme as well as H 2 O 2 and O 2 •- . Wall hydrolyzing enzymes like pectin methyl esterase and cellulase had marked downregulation both under PUT and CHT + PUT treatment. Moreover, on close observation, the combinational effects of PUT and CHT had better effects in the regulation of those enzymes as compared to individual treatment. Fruits restore higher antioxidative capacities as evident with superoxide dismutase (SOD), guaiacol peroxidases (GPX), ascorbate peroxidase (APX) catalase (CAT), glutathione peroxidase (GPX), NADPH oxidase (NOX) and glutathione reductase (GR), indicating their roles on fruit coat softening. Finally, the treatment of PUT and CHT in combination increased shelf life vis-à-vis the quality of fruit., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Since the onslaught of SARS-CoV-2, the research community has been searching for a vaccine to fight against this virus. However, during this period, the virus has mutated to adapt to the different environmental conditions in the world and made the task of vaccine design more challenging. In this situation, the identification of virus strains is very much timely and important task. We have performed genome-wide analysis of 10664 SARS-CoV-2 genomes of 73 countries to identify and prepare a Single Nucleotide Polymorphism (SNP) dataset of SARS-CoV-2. Thereafter, with the use of this SNP data, the advantage of hierarchical clustering is taken care of in such a way so that Average Linkage and Complete Linkage with Jaccard and Hamming distance functions are applied separately in order to identify the virus strains as clusters present in the SNP data. In this regard, the consensus of both the clustering results are also considered while Silhouette index is used as a cluster validity index to measure the goodness of the clusters as well to determine the number of clusters or virus strains. As a result, we have identified five major clusters or virus strains present worldwide. Apart from quantitative measures, these clusters are also visualized using Visual Assessment of Tendency (VAT) plot. The evolution of these clusters are also shown. Furthermore, top 10 signature SNPs are identified in each cluster and the non-synonymous signature SNPs are visualised in the respective protein structures. Also, the sequence and structural homology-based prediction along with the protein structural stability of these non-synonymous signature SNPs are reported in order to judge the characteristics of the identified clusters. As a consequence, T85I, Q57H and R203M in NSP2, ORF3a and Nucleocapsid respectively are found to be responsible for Cluster 1 as they are damaging and unstable non-synonymous signature SNPs. Similarly, F506L and S507C in Exon are responsible for both Clusters 3 and 4 while Clusters 2 and 5 do not exhibit such behaviour due to the absence of any non-synonymous signature SNPs. In addition to all these, the code, SNP dataset, 10664 labelled SARS-CoV-2 strains and additional results as supplementary are provided through our website for further use., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The pandemic due to novel coronavirus, SARS-CoV-2 is a serious global concern now. More than thousand new COVID-19 infections are getting reported daily for this virus across the globe. Thus, the medical research communities are trying to find the remedy to restrict the spreading of this virus, while the vaccine development work is still under research in parallel. In such critical situation, not only the medical research community, but also the scientists in different fields like microbiology, pharmacy, bioinformatics and data science are also sharing effort to accelerate the process of vaccine development, virus prediction, forecasting the transmissible probability and reproduction cases of virus for social awareness. With the similar context, in this article, we have studied sequence variability of the virus primarily focusing on three aspects: (a) sequence variability among SARS-CoV-1, MERS-CoV and SARS-CoV-2 in human host, which are in the same coronavirus family, (b) sequence variability of SARS-CoV-2 in human host for 54 different countries and (c) sequence variability between coronavirus family and country specific SARS-CoV-2 sequences in human host. For this purpose, as a case study, we have performed topological analysis of 2391 global genomic sequences of SARS-CoV-2 in association with SARS-CoV-1 and MERS-CoV using an integrated semi-alignment based computational technique. The results of the semi-alignment based technique are experimentally and statistically found similar to alignment based technique and computationally faster. Moreover, the outcome of this analysis can help to identify the nations with homogeneous SARS-CoV-2 sequences, so that same vaccine can be applied to their heterogeneous human population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

SARS-CoV-2 has a high transmission rate and shows frequent mutations, thus making vaccine development an arduous task. However, researchers around the globe are working hard to find a solution e.g. synthetic vaccine. Here, we have performed genome-wide analysis of 566 Indian SARS-CoV-2 genomes to extract the potential conserved regions for identifying peptide based synthetic vaccines, viz. epitopes with high immunogenicity and antigenicity. In this regard, different multiple sequence alignment techniques are used to align the SARS-CoV-2 genomes separately. Subsequently, consensus conserved regions are identified after finding the conserved regions from each aligned result of alignment techniques. Further, the consensus conserved regions are refined considering that their lengths are greater than or equal to 60nt and their corresponding proteins are devoid of any stop codons. Subsequently, their specificity as query coverage are verified using Nucleotide BLAST. Finally, with these consensus conserved regions, T-cell and B-cell epitopes are identified based on their immunogenic and antigenic scores which are then used to rank the conserved regions. As a result, we have ranked 23 consensus conserved regions that are associated with different proteins. This ranking also resulted in 34 MHC-I and 37 MHC-II restricted T-cell epitopes with 16 and 19 unique HLA alleles and 29 B-cell epitopes. After ranking, the consensus conserved region from NSP3 gene is obtained that is highly immunogenic and antigenic. In order to judge the relevance of the identified epitopes, the physico-chemical properties and binding conformation of the MHC-I and MHC-II restricted T-cell epitopes are shown with respect to HLA alleles., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a threat to the human population and has created a worldwide pandemic. Daily thousands of people are getting affected by the SARS-CoV-2 virus; India being no exception. In this situation, there is no doubt that vaccine is the primary prevention strategy to contain the wave of COVID-19 pandemic. In this regard, genome-wide analysis of SARS-CoV-2 is important to understand its genetic variability. This has motivated us to analyse 566 Indian SARS-CoV-2 sequences using multiple sequence alignment techniques viz. ClustalW, MUSCLE, ClustalO and MAFFT to align and subsequently identify the lists of mutations as substitution, deletion, insertion and SNP. Thereafter, a consensus of these results, called as Consensus Multiple Sequence Alignment (CMSA), is prepared to have the final list of mutations so that the advantages of all four alignment techniques can be preserved. The analysis shows 767, 2025 and 54 unique substitutions, deletions and SNPs in Indian SARS-CoV-2 genomes. More precisely, out of 54 SNPs, 4 SNPs are present close to the 60% of the virus population. The results of this experiment can be useful for virus classification, designing and defining the dose of vaccine for the Indian population., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The wave of COVID-19 is a big threat to the human population. Presently, the world is going through different phases of lock down in order to stop this wave of pandemic; India being no exception. We have also started the lock down on 23rd March 2020. In this current situation, apart from social distancing only a vaccine can be the proper solution to serve the population of human being. Thus it is important for all the nations to perform the genome-wide analysis in order to identify the genetic variation in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) so that proper vaccine can be designed. This fast motivated us to analyze publicly available 566 Indian complete or near complete SARS-CoV-2 genomes to find the mutation points as substitution, deletion and insertion. In this regard, we have performed the multiple sequence alignment in presence of reference sequence from NCBI. After the alignment, a consensus sequence is built to analyze each genome in order to identify the mutation points. As a consequence, we have found 933 substitutions, 2449 deletions and 2 insertions, in total 3384 unique mutation points, in 566 genomes across 29.9 K bp. Further, it has been classified into three groups as 100 clusters of mutations (mostly deletions), 1609 point mutations as substitution, deletion and insertion and 64 SNPs. These outcomes are visualized using BioCircos and bar plots as well as plotting entropy value of each genomic location. Moreover, phylogenetic analysis has also been performed to see the evolution of SARS-CoV-2 virus in India. It also shows the wide variation in tree which indeed vivid in genomic analysis. Finally, these SNPs can be the useful target for virus classification, designing and defining the effective dose of vaccine for the heterogeneous population., (Copyright © 2020 Elsevier B.V. All rights reserved.)