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Omicron, another SARS-CoV-2 variant, has been recorded and reported as a VoC. It has already spread across >30 countries and is a highly mutated variant. We tried to understand the role of mutations in the investigated variants by comparison with previous characterized VoC. We have mapped the mutations in Omicron S-glycoprotein's secondary and tertiary structure landscape using bioinformatics tools and statistical software and developed different models. In addition, we analyzed the effect of diverse mutations in antibody binding regions of the S-glycoprotein on the binding affinity of the investigated antibodies. This study has chosen eight significant mutations in Omicron (D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H G496S), and seven of them are located in the RBD region. We also performed a comparative analysis of the ΔΔG score of these mutations to understand the stabilizing or destabilizing properties of the investigated mutations. The analysis outcome shows that D614G, Q493K, and S477N mutations are stable mutations with ΔΔG scores of 0.351 kcal/mol, 0.470 kcal/mol, and 0.628 kcal/mol, respectively, according to DynaMut estimations. While other mutations (E484A, N501Y, K417N, Y505H, G496S) showed destabilizing results. The D614G, E484A, N501Y, K417N, Y505H, and G496S mutations increased the molecular flexibility of S-glycoprotein to interact with the ACE2 receptor, increasing the variant's infectivity. Our study will contribute to research on the SARS-CoV-2 variant, Omicron, by providing information on the mutational pattern and exciting properties of these eight significant mutations, such as antibody escape and infectivity quotient (stabilizing or destabilizing; increased or decreased molecular flexibility of S-glycoprotein to interact with the human ACE2 receptor). [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, one of the biggest challenges was the continuous evolution of SARS-CoV-2 through various mutations. This has resulted in the emergence of several variants and subvariants. The escape mutations are reported as significant mutations in several variants and subvariants responsible for immune, antibody, and nAb escape. It has been reported that FLip mutations (L455F and F456L) in the spike RBD are responsible for immune evasion and antibody escape. Recently, WHO has included a new SARS-CoV-2 VOI, JN.1 lineage, a descendent of BA.2.86. The variant is reported from more than 41 countries, including France, the USA, Canada, the UK, Singapore, Sweden, and India. It contains FLip mutations in the spike protein in RBD (L455F and F456L). The risk assessment of the variant by WHO shows it has increased transmission, immune escape, and antibody escape due to the mutations. The article illustrated that FLip mutations in RBD (L455F and F456L) are responsible for augmented transmission and immune and antibody escape. [ABSTRACT FROM AUTHOR]

Since September 2020, the SARS-CoV-2 variants have gained their dominance worldwide, especially in Kenya, Italy, France, the UK, Turkey, Indonesia, India, Finland, Ireland, Singapore, Denmark, Germany, and Portugal. In this study, we developed a model on the frequency of delta variants across 28 countries (R²= 0.1497), displaying the inheritance of mutations during the generation of the delta variants with 123,526 haplotypes. The country-wise haplotype network showed the distribution of haplotypes in USA (10,174), Denmark (5,637), India (4,089), Germany (2,350), Netherlands (1,899), Sweden (1,791), Italy (1,720), France (1,293), Ireland (1,257), Belgium (1,207), Singapore (1,193), Portugal (1,184) and Spain (1,133). Our analysis shows the highest haplotype in Europe with 84% and the lowest in Australia with 0.00001%. A model of scatter plot was generated with a regression line which provided the estimated rate of mutation, including 24.048 substitutions yearly. Our study concluded that the high global prevalence of the delta variants is due to a high frequency of infectivity, supporting the paradigm shift of the viral variants. [ABSTRACT FROM AUTHOR]

Several clinical trials started during the COVID-19 pandemic to discover effective therapeutics led to identify a few candidates from the major clinical trials. However, in the past several months, quite a few SARS-CoV-2 variants have emerged with significant mutations. Major mutations in the S-glycoprotein and other parts of the genome have led to the antibody's escape to small molecule-based therapeutic resistance. The mutations in S-glycoprotein trigger the antibody escape/resistance, and mutations in RdRp might cause remdesivir resistance. The article illustrates emerging mutations that have resulted in antibody escape to therapeutics resistance. In this direction, the article illustrates presently developed neutralizing antibodies (with their preclinical, clinical stages) and antibody escapes and associated mutations. Finally, owing to the RdRp mutations, the antiviral small molecules resistance is illustrated. [ABSTRACT FROM AUTHOR]

Presently, immunoinformatics and bioinformatics approaches are contributing actively to COVID-19 vaccine research. The first immunoinformatics-based vaccine construct against SARS-CoV-2 was published in February 2020. Following this, immunoinformatics and bioinformatics approaches have created a new direction in COVID-19 vaccine research. Several researchers have designed the next-generation COVID-19 vaccines using these approaches. Presently, immunoinformatics has accelerated immunology research immensely in the area of COVID-19. Hence, we have tried to depict the current scenario of immunoinformatics and bioinformatics in COVID-19 vaccine research. [ABSTRACT FROM AUTHOR]

The Ebola virus disease is a deadly pathogenic disease caused by the Ebola virus. It has been observed that this disease causes a high case-fatality rate. Several species of this virus were detected from the genus Ebola virus. Among them, four species of this virus (Ebola, Taï Forest, Sudan, and Bundibugyo) caused disease in humans. Scientists are now focusing on the various therapeutic developments for the treatment of this disease. This article has attempted to depict the development of the entire therapeutic scenario of this disease. In addition, the article tried to illustrate the developmental strategy of the different therapeutics such as small-molecule inhibitors, small interfering RNAs, antibodies, ion channel inhibitors, interferons, and combination therapy against Ebola virus disease. Presently, two monoclonal antibodies (REGN-EB3 and mAb114) showed better efficacy in the Pamoja tuLinde Maisha trial and received approval from the United States Food and Drug Administration. However, scientists should focus on developing more economic therapeutics. [ABSTRACT FROM AUTHOR]

Recently, India is at risk due to the exponential rising of COVID-19 infection, which generated a second wave. This infection rise may affect the vaccination program in India, and it can also affect vaccine production. In this manuscript, we have discussed the psychosocial and political factors that have driven the current wave of India. We have also tried to depict the psychosocial and political obstacles that are impairing the vaccination program. [ABSTRACT FROM AUTHOR]

• We discussed immunoinformatics approaches for SARS-CoV-2 vaccine development. • Different topics such as T cell and B cell epitopes, their identification and characterization for vaccine development against SARS-CoV-2 were discussed. • We also summarize a variety of infectious pathogens and diseases where immunoinformatics studies were applied. • Different immunoinformatics tools were enlisted for SARS-CoV-2 vaccine development. Presently, immunoinformatics is playing a significant role in epitope identification and vaccine designing for various critical diseases. Using immunoinformatics, several scientists are trying to identify and characterize T cell and B cell epitopes as well as design peptide-based vaccine against SARS-CoV-2. In this review article, we have tried to discuss the importance in adaptive immunity and its significance for designing the SARS-CoV-2 vaccine. Moreover, we have attempted to illustrate several significant key points for utilizing immunoinformatics for vaccine designing, such as the criteria for selection and identification of epitopes, T cell epitope, and B cell epitope prediction and different emerging tools/databases for immunoinformatics. In the current scenario, a few immunoinformatics studies have been performed for various infectious pathogens and related diseases. Thus, we have also summarized and included these current immunoinformatics studies in this review article. Finally, we have discussed about the probable T cell and B cell epitopes and their identification and characterization for vaccine designing against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

miRNAs, a class of small endogenous RNAs, are one of the essential biopharmaceuticals which are in commercial spans as next-generation medicine in recent times. A snapshot of the current scenario regarding the miRNAs as biopharmaceuticals have been discussed. In this work, biopharmaceutical companies working with miRNAs and the current status of preclinical/clinical trials about miRNA therapeutics have been reviewed. Finally, recent updates on the absorption, distribution, metabolism, and excretion (ADME), as well as a delivery system of miRNAs, have been illustrated. [ABSTRACT FROM AUTHOR]

The diverse, evolutionary architectures of proteins can be regarded as molecular fossils, tracing a historical path that marks important milestones across life. The B1-subfamily of GPCRs (G-protein-coupled receptors) are medically significant proteins that comprise 15 transmembrane receptor proteins in Homo sapiens. These proteins control the intracellular concentration of cyclic AMP as well as various vital processes in the body. However, little is known about the evolutionary correlation and conservational blueprint of this GPCR subfamily. We performed a comprehensive analysis to understand the evolutionary architecture among 13 members of the B1-subfamily. Multiple sequence alignment analysis exhibited six multiple sequence aligned blocks and five highly aligned blocks. Molecular phylogenetics indicated that CRHR1 and CRHR2 share a typical ancestral relationship and are siblings in 100% bootstrap replications with a total of 24 nodes observed in the cladogram. CRHR2 has the maximum number of extremely conserved amino acids followed by ADCYAP1R1. The longest continuous number sequence logos (74) were found between sequence location 349 and 423, and consequently, the maximum and minimum logo height recorded was 3.6 bits and 0.18 bits, respectively. Finally, to understand the model and pattern of evolutionary relatedness, the conservation blueprint, and the diversification among the members of a protein family, GPCR distribution from several species throughout the animal kingdom was analysed. Together, the study provides an evolutionary insight and offers a rapid method to explore the potential of depicting the evolutionary relationship, conservation blueprint, and diversification among the B1-subfamily of GPCRs using bioinformatics, algorithm analysis, and mathematical models. [ABSTRACT FROM AUTHOR]

Phosphoinositide 3-kinase (PI3K) is an essential regulatory protein of the insulin signaling pathway and several other pathways that govern cell survival, cell proliferation, cell differentiation and oncogene regulation. The protein has main two subunits; regulatory p85 and catalytic p110. Other regulatory subunits are p50, p55. The catalytic activity of p110 is stabilized by the regulatory subunit p85α. This regulatory subunit is composed of five domains; the SH3, BCR-homology (BH), N-terminal SH2 (nSH2), C-terminal SH2 (cSH2), and inter-SH2 (iSH2). In the current study, we executed comparative analysis of the computational proteomic and molecular evolution of these five domains. Our results reveal that faster and more cost-effective methods for forming intricate relationships between the domains are worth pursuing according to vital proteomic parameters such as physico-chemical properties, evolution and post-translational modification (PTM). The results show variation instability, grand average of hydrophobicity (GRAVY), aliphatic index, globularity, PTM among the five domains, and strongly indicate a likeness between the nSH2 and cSH2 domains. The study provides vital information for the structural and functional aspects of PI3K regulatory subunit p85α. Many of these property changes might be defined as protein–protein interactions, protein folding structures and structure–function correlations in future. [ABSTRACT FROM AUTHOR]

The recent development of next‐generation sequencing technologies has offered valuable insights into individual cells. This technology is centered on the characterization of single cells for epigenomics, genomics, and transcriptomics. Ever since the first report appeared in 2009, the single‐cell RNA‐sequencing saga started to explore deeper into the mechanics intrigued within a single cell. microRNA (miRNA) has been increasingly recognized as an essential molecule triggering an additional layer for gene regulation. Therefore, single‐cell sequencing of miRNAs is crucial to explore the logical riddles surrounding the epigenomics, genomics, and transcriptomics of an individual cell. Scientists from the Vienna Biocenter Campus have lately performed single‐cell sequencing of miRNAs in the fly, Drosophila, and nematode, Caenorhabditis elegans. In this review, we present the latest scientific explorations supported by all‐inclusive data on this novel subject matter of next‐generation sequencing. [ABSTRACT FROM AUTHOR]

The COVID-19 outbreak is a disaster now throughout the world. To stop this outbreak, we appeal through the paper for extensive partnership, collaboration and teamwork among the all levels of workers such as scientist, doctors, medical professionals, social workers, policy makers, governments, pharmaceutical firms, funding aid agencies to stop the pandemic immediately. [ABSTRACT FROM AUTHOR]

Objective: Druggability of a target protein depends on the interacting micro-environment between the target protein and drugs. Therefore, a precise knowledge of the interacting micro-environment between the target protein and drugs is requisite for drug discovery process. To understand such micro-environment, we performed in silico interaction analysis between a human target protein, Dipeptidyl Peptidase-IV (DPP-4), and three anti-diabetic drugs (saxagliptin, linagliptin and vildagliptin). Materials and Methods: During the theoretical and bioinformatics analysis of micro-environmental properties, we performed drug-likeness study, protein active site predictions, docking analysis and residual interactions with the protein-drug interface. Micro-environmental landscape properties were evaluated through various parameters such as binding energy, intermolecular energy, electrostatic energy, van der Waals'+H-bond+desolvo energy (EVHD) and ligand efficiency (LE) using different in silico methods. For this study, we have used several servers and software, such as Molsoft prediction server, CASTp server, AutoDock software and LIGPLOT server. Results: Through micro-environmental study, highest log P value was observed for linagliptin (1.07). Lowest binding energy was also observed for linagliptin with DPP-4 in the binding plot. We also identified the number of H-bonds and residues involved in the hydrophobic interactions between the DPP-4 and the anti-diabetic drugs. During interaction, two H-bonds and nine residues, two H-bonds and eleven residues as well as four H-bonds and nine residues were found between the saxagliptin, linagliptin as well as vildagliptin cases and DPP-4, respectively. Conclusion: Our in silico data obtained for drug-target interactions and micro-environmental signature demonstrates linagliptin as the most stable interacting drug among the tested anti-diabetic medicines. [ABSTRACT FROM AUTHOR]

Presently, nanotechnology is a multi-trillion dollar business sector that covers a wide range of industries, such as medicine, electronics and chemistry. In the current era, the commercial transition of nanotechnology from research level to industrial level is stimulating the world's total economic growth. However, commercialization of nanoparticles might offer possible risks once they are liberated in the environment. In recent years, the use of zebrafish (Danio rerio) as an established animal model system for nanoparticle toxicity assay is growing exponentially. In the current in-depth review, we discuss the recent research approaches employing adult zebrafish and their embryos for nanoparticle toxicity assessment. Different types of parameters are being discussed here which are used to evaluate nanoparticle toxicity such as hatching achievement rate, developmental malformation of organs, damage in gill and skin, abnormal behavior (movement impairment), immunotoxicity, genotoxicity or gene expression, neurotoxicity, endocrine system disruption, reproduction toxicity and finally mortality. Furthermore, we have also highlighted the toxic effect of different nanoparticles such as silver nanoparticle, gold nanoparticle, and metal oxide nanoparticles (TiO2, Al2O3, CuO, NiO and ZnO). At the end, future directions of zebrafish model and relevant assays to study nanoparticle toxicity have also been argued. [ABSTRACT FROM AUTHOR]

• Recently, the emergence of MPX has created a global threat, and vaccination is one of the significant ways to fight against the virus. • The article describes the important points and issues for vaccines and vaccinations related to the MPXV. • It also illustrates significant research on the MPXV, especially smallpox vaccines, and its outcome in MPX infection. • Vaccination preparedness has been illustrated in various countries like the USA, UK, Canada, Denmark, Germany, etc. The recent emergence of monkeypox (MPX) has created a global threat. The number of infected and suspected cases of MPX is increasing in different parts of the world, especially in non-African countries. However, vaccines are available to fight against this disease. It has been observed that smallpox vaccines can be used to protect against MPX. The present article highlights the significant points and various issues for vaccines and vaccinations that should be considered related to MPX. This paper illustrates current vaccines for smallpox that can be utilized to protect against MPX infection. The article also describes the different significant research on MPXV, especially smallpox vaccines, and its outcome in MPX infection. We have also tried to depict the smallpox vaccination eradication model through the statistical interface using smallpox eradication data from Central and West Africa between 1967 and 1972. We suggest that these models might be helpful for the eradication of MPX in the middle to low-economic countries. Simultaneously, we have also discussed vaccination preparedness in different countries like the USA, UK, Canada, Denmark, Germany, etc. Our report might be helpful to scientists and policymakers in understanding the vaccines and vaccination against MPX and formulating effective strategies to fight against the disease. [ABSTRACT FROM AUTHOR]

In the recent advancement of cancer therapy, mortality of the immortal cancer cells begins to decline, and it shows great promise for the chemotherapy regimen supported by targeted therapy. In this post-genomic era boosted by the discovery of microRNA (miRNA), it has been understood that miRNA regulates gene expression at the post-transcriptional level. On the other hand, some studies have also indicated that miRNA expression level has changed during the treatment of chemotherapy. Data based on various previous studies, we propose that the chemotherapeutic agents modulate miRNA expression that might perform anticancerous activities through cellular changes such as DNA repair, cell cycle arrest, or apoptosis. [ABSTRACT FROM AUTHOR]

We performed canonical correlation analysis as an unsupervised statistical tool to describe related views of the same semantic object for identifying patterns. A pattern recognition technique based on canonical correlation analysis (CCA) was proposed for finding required genetic code in the DNA sequence. Two related but different objects were considered: one was a particular pattern, and other was test DNA sequence. CCA found correlations between two observations of the same semantic pattern and test sequence. It is concluded that the relationship possesses maximum value in the position where the pattern exists. As a case study, the potential of CCA was demonstrated on the sequence found from HIV-1 preferred integration sites. The subsequences on the left and right flanking from the integration site were considered as the two views, and statistically significant relationships were established between these two views to elucidate the viral preference as an important factor for the correlation. [ABSTRACT FROM AUTHOR]

The massive increase in COVID-19 infection had generated a second wave in India during May–June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant. This study was performed in three directions to understand the pandemic response of the two emerging variants. First, we served comparative genomics, such as genome sequence submission patterns, mutational landscapes, and structural landscapes of significant mutations (N501Y, D614G, L452R, E484Q, and P681R). Second, we performed evolutionary epidemiology using molecular phylogenetics, scatter plots of the cluster evaluation, country-wise transmission pattern, and frequency pattern. Third, the receptor binding pattern was analyzed using the Wuhan reference strain and the other two variants. The study analyzed the country-wise and region-wise genome sequences and their submission pattern, molecular phylogenetics, scatter plot of the cluster evaluation, country-wise geographical distribution and transmission pattern, frequency pattern, entropy diversity, and mutational landscape of the two variants. The structural pattern was analyzed in the N501Y, D614G L452R, E484Q, and P681R mutations. The study found increased molecular interactivity between hACE2-RBD binding of B.1.1.7 and B.1.617.2 compared to the Wuhan reference strain. Our receptor binding analysis showed a similar indication pattern for hACE2-RBD of these two variants. However, B.1.617.2 offers slightly better stability in the hACE2-RBD binding pattern through MD simulation than B.1.1.7. The increased hACE2-RBD binding pattern of B.1.1.7 and B.1.617.2 might help to increase the infectivity compared to the Wuhan reference strain. [Display omitted] • Comparative genomics of two emerging SARS-CoV-2 variants (B.1.1.7 and B. 1.617.2). • Evolutionary epidemiology, geographical distribution and country-wise transmission patterns of study of Alpha.1.1.7 and Delta. 1.617.2. • Landscape of significant mutations such as L452R, E484Q, N501Y, D614G and P681R. • RBD-hACE2 receptor binding pattern analysis in B.1.1.7 and B. 1.617.2 compare to Wuhan reference strain. [ABSTRACT FROM AUTHOR]

During the last two decades, the DNA barcode development towards microbial community has increased dramatically. DNA barcode development is related to error-free and quick species identification which aid in understanding the microbial biodiversity, as well as the diseases related to microbial species. Here, we seek to evaluate the so-called barcoding initiatives for the microbial communities and the emerging trends in this field. In this paper, we describe the development of DNA marker-based DNA barcoding system, comparison between routine species identification and DNA barcode, and microbial biodiversity and DNA barcode for microbial communities. Two major topics, such as the molecular diversity of viruses and barcode for viruses have been discussed at the same time. We demonstrate the current status and the maker of DNA barcode for bacteria, algae, fungi, and protozoa. Furthermore, we argue about the promises, limitations, and present and future challenges of microbial barcode development. [ABSTRACT FROM AUTHOR]

Aim Comparative structural bioinformatic analysis of the conserved domains and amino acid residues, binding grooves of the tumor necrosis factor (TNF)α and β in order to elucidate structure-based inhibitor development was conducted. Methods We carried out the bioinformatics study of TNF proteins at the Department of Bio-informatics (Galgotias University, India) between June and December 2012. TNFα and TNF-β functional protein sequences in FASTA format were obtained from the NCBI database for analysis. The online tool ClustalW from the European Bioinformatic Institute was used for multiple sequence alignment to record similarities. The Jmol server was used for 3D visualization of alpha helix, beta sheet and loops of TNF proteins. The PyMOL molecular visualization system was used to generate surface cavity and to identify binding grooves of TNF proteins. Results This study showed highly conserved amino acids residues such as LYS11, PRO12, ALA14, HIS15, VAL50, PRO51, GLY54, LEU55, TYR56, LEU57, TYR59, SER60, GLN61, GLY122, VAL123, PHE124, PHE152, and GLY153 are consequent amino acids in TNF-α while residues such as ALA31, HIS32, SER77, GLN78, PHE166, and GLY167 are consequent amino acids in TNF-β. Surface cavity and binding grooves showed TNF-β with larger surface cavities than TNF-α with higher chances for drug development since small drug-like molecules can bind easily into the groove. Conclusion The results illustrate the structure of TNF proteins and the novel findings may guide future research on TNF and in the process of assisting the optimization of the pharmacological properties involving the two crucial proteins. [ABSTRACT FROM AUTHOR]

In human, Wnt/β-catenin signaling pathway plays a significant role in cell growth, cell development, and disease pathogenesis. Four human (Rspo)s are known to activate canonicalWnt/β-catenin signaling pathway. Presently, (Rspo)s serve as therapeutic target for several human diseases. Henceforth, basic understanding about themolecular properties of (Rspo)s is essential. We approached this issue by interpreting the biochemical and biophysical properties alongwithmolecular evolution of (Rspo)s thorough computational algorithm methods. Our analysis shows that signal peptide length is roughly similar in (Rspo)s family along with similarity in aa distribution pattern. In Rspo3, four N-glycosylation sites were noted. All members are hydrophilic in nature and showed alike GRAVY values, approximately. Conversely, Rspo3 contains the maximum positively charged residues while Rspo4 includes the lowest. Four highly aligned blocks were recorded through Gblocks. Phylogenetic analysis shows Rspo4 is being rooted with Rspo2 and similarly Rspo3 and Rspo1 have the common point of origin. Through phylogenomics study, we developed a phylogenetic tree of sixty proteins (n= 60) with the orthologs and paralogs seed sequences. Protein-protein network was also illustrated. Results demonstrated in our study may help the future researchers to unfold significant physiological and therapeutic properties of (Rspo)s in various disease models. [ABSTRACT FROM AUTHOR]

Objective: Research related to induce pluripotent stem (iPS) cell generation has increased rapidly in recent years. Six transcription factors, namely OCT4, SOX2, C-MYC, KLF4, NANOG, and LIN28 have been widely used for iPS cell generation. As there is a lack of data on intra- and inter-networking among these six different transcription factors, the objective of this study is to analyze the intra- and inter-networks between them using bioinformatics. Materials and Methods:In this computational biology study, we used AminoNet, MATLAB to examine networking between the six different transcription factors. The directed network was constructed using MATLAB programming and the distance between nodes was estimated using a phylogram. The protein-protein interactions between the nuclear reprogramming factors was performed using the software STRING. Results: The relationship between C-MYC and NANOG was depicted using a phylogenetic tree and the sequence analysis showed OCT4, C-MYC, NANOG, and SOX2 together share a common evolutionary origin. Conclusion: This study has shown an innovative rapid method for the analysis of intra and inter-networking among nuclear reprogramming factors. Data presented may aid researchers to understand the complex regulatory networks involving iPS cell generation. [ABSTRACT FROM AUTHOR]

Understanding and predicting the significance of novel genetic variants revealed by DNA sequencing is a major challenge to integrate and interpret in medical genetics with medical practice. Recent studies have afforded significant advances in characterization and predicting the association of single nucleotide polymorphisms in human TERT with various disorders, but the results remain inconclusive. In this context, a comparative study between disease causing and novel mutations in hTERT gene was performed computationally. Out of 59 missense mutations, five variants were predicted to be less stable with the most deleterious effect on hTERT gene by in silico tools, in which two mutations (L584W and M970T) were not previously reported to be involved in any of the human disorders. To get insight into the structural and functional impact due to the mutation, docking study and interaction analysis was performed followed by 6 ns molecular dynamics simulation. These results may provide new perspectives for the targeted drug discovery in the coming future. [ABSTRACT FROM AUTHOR]

Cluster of differentiation (CD) is a group of proteins with highly immunological and medical importance, and some are established therapeutics. These membrane proteins are used to investigate of cell surface molecules of blood cells especially WBC. We selected a population of fifteen members with most medical importance, which includes CD2, CD4, CD5, CD6, CD7, CD9, CD14, CD16, CD19, CD22, CD28, CD33, CD36, CD38, and CD44 and performed in silico analysis using algorithm analysis and mathematical models. The results suggest that LEU (L) is well aligned. CD16 is rooted with CD22 and likewise, CD4 is closely related to CD44. Notably, highest number of highly conserved amino acids is recorded in CD22. WebLogo were formed up to 350 amino acid position and Met (M) is found to be tallest logo. Our results would be useful for upcoming researchers to obtain fundamental idea about the particular regions CD proteins which is having the structural and functional significance related to the evolutionary biology. [ABSTRACT FROM AUTHOR]

Abstract: Using computational biology, we have depicted the insulin phylogenetics. We have also analyzed the sequence alignment and sequence logos formation for both the insulin chain A and B for three groups namely, the mammalian group, vertebrates group and fish group. We have also analyzed cladograms of insulin for the mammalian group. In accordance with that path lengths, matrix for distance analysis, matching representation of nodes of the cladogram and dissimilarity between two nodes have been performed for both of the A and B chains of the mammalian group. Our results show that 12 amino acid residues (GlyA1, IleA2, ValA3, TyrA19, CysA20, AsnA21, LeuB6, GlyB8, LeuB11, ValB12, GlyB23 and PheB24) are highly conserved for all groups and among them some (GlyA1, IleA2, ValA3);(TyrA19, CysA20, AsnA21) are continuous. This study shows a rapid method to calculate the amino acid sequences in terms of evolutionary conservation rates as well as molecular phylogenetics. [Copyright &y& Elsevier]

All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that include regeneration, multicellularity and coloniality. Stem cells have attracted the attention of biologists and medical scientists for a long time. These provide materials for regenerative medicine. We review in this paper, the link between modern stem cell research and early studies in ancient organisms. It also outlines details on stem cells in the light of evolution with an emphasis on their regeneration potential, coloniality and multicellularity. The information provided might be of use to molecular biologists, medical scientists and developmental biologists who are engaged in integrated research involving the stem cells. [ABSTRACT FROM AUTHOR]

Insulin receptor substrate (IRS) harbors proteins such as IRS1, IRS2, IRS3, IRS4, IRS5 and IRS6. These key proteins act as vital downstream regulators in the insulin signaling pathway. However, little is known about the evolutionary relationship among the IRS family members. This study explores the potential to depict the evolutionary relationship among the IRS family using bioinformatics, algorithm analysis and mathematical models. [ABSTRACT FROM AUTHOR]

The type 2 diabetes has increased rapidly in recent years throughout the world. The insulin signal transduction mechanism gets disrupted sometimes and it's known as insulin-resistance. It is one of the primary causes associated with type-2 diabetes. The signaling mechanisms involved several proteins that include 7 major functional proteins such as INS, INSR, IRS1, IRS2, PIK3CA, Akt2, and GLUT4. Using these 7 principal proteins, multiple sequences alignment has been created. The scores between sequences also have been developed. We have constructed a phylogenetic tree and modified it with node and distance. Besides, we have generated sequence logos and ultimately developed the protein-protein interaction network. The small insulin signal transduction protein arrangement shows complex network between the functional proteins. [ABSTRACT FROM AUTHOR]

Abstract: India''s biotechnology industry has been growing towards new heights in conjunction with the recent economic outburst. The country has the potential to revolutionize biopharmaceutical and healthcare sectors. In this review, we have highlighted the achievements of India''s biotechnology industry, especially biopharmaceutical and healthcare sectors that include therapeutics, diagnostics, stem cell research, human healthcare related bioinformatics and animal health care. We have also described regulatory mechanisms involved in India''s health care biotech including manpower development. [Copyright &y& Elsevier]

In recent years, a total of seven human pathogenic coronaviruses (HCoVs) strains were identified, i.e., SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Here, we performed an analysis of the protease recognition sites and antigenic variation of the S-protein of these HCoVs. We showed tissue-specific expression pattern, functions, and a number of recognition sites of proteases in S-proteins from seven strains of HCoVs. In the case of SARS-CoV-2, we found two new protease recognition sites, each of calpain-2, pepsin-A, and caspase-8, and one new protease recognition site each of caspase-6, caspase-3, and furin. Our antigenic mapping study of the S-protein of these HCoVs showed that the SARS-CoV-2 virus strain has the most potent antigenic epitopes (highest antigenicity score with maximum numbers of epitope regions). Additionally, the other six strains of HCoVs show common antigenic epitopes (both B-cell and T-cell), with low antigenicity scores compared to SARS-CoV-2. We suggest that the molecular evolution of structural proteins of human CoV can be classified, such as (i) HCoV-NL63 and HCoV-229E, (ii) SARS-CoV-2, and SARS-CoV and (iii) HCoV-OC43 and HCoV-HKU1. In conclusion, we can presume that our study might help to prepare the interventions for the possible HCoVs outbreaks in the future. • Analysis of the protease recognition sites and antigenic variation of S-protein of seven HCoVs. • Tissue specific- expression pattern analysis of the proteases of seven HCoVs. • Grouping of seven HCoVs strains through molecular phylogenetics using of S, M, E, N proteins. • Immunogenicity and conservancy analysis of common B-cell and T-cell epitopes of seven HCoVs. [ABSTRACT FROM AUTHOR]

The transdermal drug delivery system is an exceptionally safe and well-tolerable therapeutic approach that has immense potential for delivering active components against bone-related pathologies. However, its use is limited in the current clinical practices due to the low skin permeability of most active drugs in the formulation. Thus, innovations in the methodologies of skin permeation enhancement techniques are suggested to overcome this limitation. Although various transdermal drug delivery systems are studied to date, there are insufficient studies comparing the therapeutic efficacy of transdermal delivery systems to oral delivery systems. Thus, creating a decision-making dilemma between oral or transdermal therapies. Therefore, a timely review is inevitable to develop a platform for future researchers to develop next-generation transdermal drug delivery strategies against skeletal diseases that must be convenient and cost-effective for the patients with improved therapeutic efficacy. Here, we will outline the most recent strategies that can overcome the choice limitation of the drug and enhance the transdermal adsorption of various types of drugs to treat bone disorders. For the first time, in this review paper, we will highlight the preclinical and clinical studies on the different transdermal delivery methods. Thus, providing insight into the current therapeutic approaches and suggesting new directions for the advancements in transdermal drug delivery systems against bone disorders. [Display omitted] [ABSTRACT FROM AUTHOR]

A correction to the article "Can the chemotherapeutic agents performanticancer activity through miRNA expression regulation? Proposing a new hypothesis" that was published in the 2015 issue is presented.

A letter to the editor is presented in response to the article "Introduction to nanotechnology: potential applications in physical medicine and rehabilitation," in the March 2007 issue.

A letter to the editor is presented about the need for a wider partnership in the pharmaceutical industry and foreign-aid agencies to help eradicate Ebola.

Over the past decade, advancements in next generation sequencing technology have placed personalized genomic medicine upon horizon. Understanding the likelihood of disease causing mutations in complex diseases as pathogenic or neutral remains as a major task and even impossible in the structural context because of its time consuming and expensive experiments. Among the various diseases causing mutations, single nucleotide polymorphisms (SNPs) play a vital role in defining individual's susceptibility to disease and drug response. Understanding the genotype-phenotype relationship through SNPs is the first and most important step in drug research and development. Detailed understanding of the effect of SNPs on patient drug response is a key factor in the establishment of personalized medicine. In this paper, we represent a computational pipeline in anaplastic lymphoma kinase (ALK) for SNP-centred study by the application of in silico prediction methods, molecular docking, and molecular dynamics simulation approaches. Combination of computational methods provides a way in understanding the impact of deleterious mutations in altering the protein drug targets and eventually leading to variable patient's drug response. We hope this rapid and cost effective pipeline will also serve as a bridge to connect the clinicians and in silico resources in tailoring treatments to the patients' specific genotype. [ABSTRACT FROM AUTHOR]

Individuals with comorbidities (i.e., Diabetes Mellitus, hypertension, heart diseases) are more likely to develop a more severe form of coronavirus disease 2019 (COVID-19), thus, they should take necessary precautions to avoid infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its emerging variants and subvariants by getting COVID-19 vaccination and booster doses. In this regard, we used text analytics techniques, specifically Natural Language Processing (NLP), to understand the perception of Twitter users having comorbidities (diabetes, hypertension, and heart diseases) towards the COVID-19 vaccine booster doses. Understanding and identifying Twitter users’ perceptions and perspectives will help the members of medical fraternities, governments, and policymakers to frame and implement a suitable public health policy for promoting the uptake of booster shots by such vulnerable people. A total of 176,540 tweets were identified through the scrapping process to understand the perception of individuals with the mentioned comorbidities regarding the COVID-19 booster dose. From sentiment analysis, it was revealed that 57.6% out of 176,540 tweets expressed negative sentiments about the COVID-19 vaccine booster doses. The reasons for negative expressions have been found using the topic modeling approach (i.e., risk factors, fear of myocardial fibrosis, stroke, or death, and using vaccines as bio-weapons). Of note, enhancing the COVID-19 vaccination drive by administering its booster doses to more and more people is of paramount importance for rendering higher protective immunity under the current threats of recently emerging newer Omicron subvariants which are presently causing a rise in cases in a few countries, such as China and others, and might lead to a feasible new wave of the pandemic with the surge in cases at the global level. [ABSTRACT FROM AUTHOR]

In the last two years, the world encountered the SARS-CoV-2 virus, which is still dominating the population due to the absence of a viable treatment. To eradicate the global pandemic, scientists, doctors, and researchers took an exceptionally significant initiative towards the development of effective therapeutics to save many lifes. This review discusses about the single-domain antibodies (sdAbs), also called nanobodies, their structure, and their types against the infections of dreadful SARS-CoV-2 virus. A precise description highlights the nanobodies and their therapeutic application against the other selected viruses. It aims to focus on the extraordinary features of these antibodies compared to the conventional therapeutics like mAbs, convalescent plasma therapy, and vaccines. The stable structure of these nanobodies along with the suitable mechanism of action also confers greater resistance to the evolving variants with numerous mutations. The nanobodies developed against SARS-CoV-2 and its mutant variants have shown the greater neutralization potential than the primitive ones. Engineering of these specialized antibodies by modern biotechnological approaches will surely be more beneficial in treating this COVID-19 pandemic along with certain other viral infections. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative disease of the joints and is one of the leading causes of disability in adults. However, there are no key therapeutics for OA and medical treatment is based on managing the symptoms and slowing down progression of the disease. Diagnostics based on clinical examination and radiography have provided little information about metabolic changes in joint tissues, disease onset and progression. Due to lack of effective methods for early detection and evaluation of treatment outcome, the measurement of biochemical markers (biomarkers) shows promise as a prospective method aiding in disease monitoring. OA biomarkers that are present in biological fluids such as blood, urine and synovial fluid, sources that are easily isolated from body, are of particular interest. Moreover, there are increasingly more studies identifying and developing new biomarkers for OA. In this review, efforts have been made to summarize the biomarkers that have been reported in recent studies on patients. We also tried to classify biomarkers according to tissue metabolism (bone, cartilage and synovial metabolism markers), pathological pathways (inflammatory and genetic markers) and biological function (chemokines, growth factors, acute phase proteins, etc.). [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all the previously emerged variants. The numerous mutations in Omicron's viral genome and its sub-lineages attribute it a larger amount of viral fitness, owing to the alteration of the transmission and pathophysiology of the virus. With a rapid change to the viral structure, Omicron and its sub-variants, namely BA.1, BA.2, BA.3, BA.4, and BA.5, dominate the community with an ability to escape the neutralization efficiency induced by prior vaccination or infections. Similarly, several recombinant sub-variants of Omicron, namely XBB, XBD, and XBF, etc., have emerged, which a better understanding. This review mainly entails the changes to Omicron and its sub-lineages due to it having a higher number of mutations. The binding affinity, cellular entry, disease severity, infection rates, and most importantly, the immune evading potential of them are discussed in this review. A comparative analysis of the Delta variant and the other dominating variants that evolved before Omicron gives the readers an in-depth understanding of the landscape of Omicron's transmission and infection. Furthermore, this review discusses the range of neutralization abilities possessed by several approved antiviral therapeutic molecules and neutralizing antibodies which are functional against Omicron and its sub-variants. The rapid evolution of the sub-variants is causing infections, but the broader aspect of their transmission and neutralization has not been explored. Thus, the scientific community should adopt an elucidative approach to obtain a clear idea about the recently emerged sub-variants, including the recombinant variants, so that effective neutralization with vaccines and drugs can be achieved. This, in turn, will lead to a drop in the number of cases and, finally, an end to the pandemic. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the control of electronic waste in India.

• The article highlighted an overview of long COVID, significant clinical symptoms, and different long COVID clinical trials. • It illustrated different challenges and recommendations for long COVID. • The article depicted the underlying mechanisms and risk factors of long COVID. • The ongoing clinical trials that might provide future therapeutics for treating long COVID, were also highlighted. Long COVID was reported as a multi-systemic condition after the infection of SARS-CoV-2, and more than 65 million people are suffering from this disease. It has been noted that around 10% of severe SARS-CoV-2 infected individuals are suffering from the enduring effects of long COVID. The symptoms of long COVID have also been noted in several mild or asymptomatic SARS-CoV-2 infected individuals. While limited reports on clinical trials investigating new therapeutics for long COVID exist, there is an abundance of scattered information available regarding these trials. This review explores the extensive literature search, and complete clinical trial database search to map the current status of long COVID clinical trials worldwide. The study listed about 110 long COVID clinical trials. In addition to conducting extensive long COVID clinical trials, we have comprehensively presented an overview of the condition, its symptoms, notable manifestations, associated clinical trials, the unique challenges it poses, and our recommendations for addressing long COVID. [ABSTRACT FROM AUTHOR]

Objectives: Osteoporosis is regarded as a silent disorder affecting bone slowly, leading to an increased risk of fractures. Lately, selenium has been found to be associated with the acquisition and maintenance of bone health by affecting the bone remodeling process. However, the mechanism of action of selenium on bone is poorly understood. Here, the objective of this study is to examine the protective effects and mechanism of sodium selenite on the differentiation process of osteoblasts as well as under oxidative stress-induced conditions by evaluating the expression of osteoblast differentiation markers in the sodium selenite and/or hydrogen peroxide (H2O2)-treated MC3T3-E1 cell line. Materials and Methods: In this experimental study, we confirmed the inducible osteogenic effect of sodium selenite on MC3T3-E1 cells. Moreover, we investigated the recovery of expression levels of osteogenic markers of sodium selenite in H2O2-treated MC3T3-E1 cells. Results: It was observed that sodium selenite could promote alkaline phosphatase (ALP) activity and collagen synthesis in pre-osteoblasts. Also, sodium selenite enhanced the mRNA expression levels of osteogenic transcriptional factors, like osterix (OSX) and runt-related transcription factor 2 (Runx2). In addition, the terminal differentiation markers, such as osteocalcin (OCN) and collagen 1α (Col1α) were also increased after the treatment of sodium selenite. Also treatment of sodium selenite recused the H2O2-induced inhibition of osteoblastic differentiation of pre-osteoblasts cells via the WNT signaling pathway, implicating its antioxidant activity. Furthermore, sodium selenite restored the H2O2 repressed β-catenin stability and axin-2 reporter activity in MC3T3-E1 cells. Conclusion: It may be concluded that sodium selenite can stimulate bone formation and rescue the oxidative repression of osteogenesis by activating WNT signaling pathways. Further detailed studies on the role of selenium and its ability to stimulate bone formation via the WNT signaling pathway may project it as a potential therapeutic intervention for osteoporosis. [ABSTRACT FROM AUTHOR]

Some individuals with non-small-cell lung cancer (NSCLC) benefit from therapies targeting epidermal growth factor receptor (EGFR), and the characterization of a new mechanism of resistance to the EGFR-specific antibody gefitinib will provide valuable insight into how therapeutic strategies might be designed to overcome this particular resistance mechanism. The G719S and T790M mutations and their combination were involved in causing different conformational redistribution of EGFR. In the present computational study, we analyzed the impact and structural influence of G719S/T790M double mutation (DM) in EGFR with ligand (gefitinib) through molecular dynamic simulation (50 ns) and docking analysis. We observed the escalation in distance between the functional loop and activation loop with respect to T790M mutation compared to the G719S mutation. Furthermore, we confirmed that the G719S mutation causes the ligand to move closer to the hinge region, whereas T790M makes the ligand escape from the binding pocket. Obtained results provide with an explanation for the resistance induced by T790M and a vital clue for the design of drugs to combat gefitinib resistance. [ABSTRACT FROM AUTHOR]