Genome characterization, phylogenomic assessment and spatio-temporal dynamics study of highly mutated BA variants from India.

PURPOSE: The emergence of highly mutated and transmissible BA variants has caused an unprecedented surge in COVID-19 infections worldwide. Thorough analysis of its genome structure and phylogenomic evolutionary details will serve as scientific reference for future research. METHOD: Here, we have analyzed the BA variants from India using whole-genome sequencing, spike protein mutation study, spatio-temporal surveillance, phylogenomic assessment and epitope mapping. RESULTS: The predominance of BA.2/BA.2-like was observed in India during COVID-19 third wave. Genome analysis and mutation study highlighted the existence of 2128 amino acid changes within BA as compared to NC_045512.2. Presence of 23 unknown mutation sites (spanning region 61-831) were observed among the Indian BA variants as compared to the global BA strains. Unassigned probable Omicron showed the highest number of mutations (370) followed by BA.1 (104), BA.2.3 (56), and BA.2 (27). Presence of mutations 'Q493R â€‹+ â€‹Q498R â€‹+ â€‹N501Y', and 'K417 â€‹N â€‹+ â€‹E484A â€‹+ â€‹N501Y' remained exclusive to BA.2 as well as unassigned probable Omicron. The time-tree and phylogenomic network assessed the evolutionary relationship of the BA variants. Existence of 424 segregating sites and 113 parsimony informative sites within BA genomes were observed through haplotype network analysis. Epitope mapping depicted the presence of unique antigenic sites within the receptor binding domain of the BA variants that could be exploited for robust vaccine development. CONCLUSION: These findings provide important scientific insights about the nature, diversity, and evolution of Indian BA variants. The study further divulges in the avenues of therapeutic upgradation for better management and eventual eradication of COVID-19.

Genome surveillance of SARS-CoV-2 variants and their role in pathogenesis focusing on second wave of COVID-19 in India.

India had witnessed unprecedented surge in SARS-CoV-2 infections and its dire consequences during the second wave of COVID-19, but the detailed report of the epidemiological based spatiotemporal incidences of the disease is missing. In the manuscript, we have applied various statistical approaches (correlation, hierarchical clustering) to decipher the pattern of pathogenesis of the circulating VoCs responsible for surge in the incidences. B.1.617.1 (Kappa) was the predominant VoC during the early phase of the second wave, whereas, Delta (B.1.617.2) or Delta-like (AY.x) VoC constitutes majority ([Formula: see text]%) of the cases during the peak of the second wave. The correlation plot of Delta/Delta-like lineage demonstrates inverse correlation with other lineages including B.1.617.1, B.1.1.7, B.1, B.1.36.29 and B.1.36. The spatiotemporal analysis shows that most of the Indian states were affected during the peak of the second wave due to the Delta surge, and fall under the same cluster. The second cluster populated mostly by north-eastern states and the islands of India were minimally affected. The presence of signature mutations (T478K, D950N, E156G) along with L452K, D614G and P681R within the spike protein of Delta or Delta-like might cause elevation in the host cell attachment, increased transmission and altered antigenicity which in due course of time has replaced the other circulating variants.The timely assessment of new VoCs including Delta-like will provide a rationale for updating the diagnostic, vaccine development by medical industries and decision making by various agencies including government, educational institutions, and corporate industries.

Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders.

An aptamer is a short sequence of synthetic oligonucleotides which bind to their cognate target, specifically while maintaining similar or higher sensitivity compared to an antibody. The in-vitro selection of an aptamer, applying a conjoining approach of chemistry and molecular biology, is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are further modified chemically in an attempt to make them stable in biofluid, avoiding nuclease digestion and renal clearance. While the modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer applications that are currently not only restricted to in-vitro systems, but have also been used in molecular imaging for disease pathology and treatment. In the food industry, it has been used as sensor for detection of different diseases and fungal infections. In this review, we have discussed a brief history of its journey, along with applications where its role as a therapeutic plus diagnostic (theranostic) tool has been demonstrated. We have also highlighted the potential aptamer-mediated strategies for molecular targeting of COVID-19. Finally, the review focused on its future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cells and also in single cell proteomics (scProteomics) to study intra or inter-tumor heterogeneity at the protein level. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and low immunogenicity provide advantages to the aptamer over the antibody. These physical and chemical properties of aptamers render them as a strong biomedical tool for theranostic purposes over the existing ones. The significance of aptamers in human health was the key finding of this review.