In depth analysis of Cyprus-specific mutations of SARS-CoV-2 strains using computational approaches
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ABSTRACT:
SUBMITTER: Oulas A
PROVIDER: S-EPMC8590444 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The novel coronavirus pandemic that has originated from China and spread throughout the world in three months. Genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predecessor, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) play an important role in understanding the concept of genetic variation. In this paper, the genomic data accessed from National Center for Biotechnology Information (NCBI) through Molecular Evolutionary Genetic Analysis (MEGA) for statistical analysis. Firstly, the Bayesian information criterion (BIC) and Akaike information criterion (AICc) are used to evaluate the best substitution pattern. Secondly, the maximum likelihood method used to estimate of transition/transversions (R) through Kimura-2, Tamura-3, Hasegawa-Kishino-Yano, and Tamura-Nei nucleotide substitutions model. Thirdly and finally nucleotide frequencies computed based on genomic data of NCBI. The results indicate that general times reversible model has the lowest BIC and AICc score 347,394 and 347,287, respectively. The transition/transversions bias for nucleotide substitutions models varies from 0.56 to 0.59 in MEGA output. The average nitrogenous bases frequency of U, C, A, and G are 31.74, 19.48, 28.04, and 20.74, respectively in percentages. Overall the genomic data analysis of SARS-CoV-2, SARS-CoV, and MERS-CoV highlights the close genetic relationship.
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Project description:COVID-19 caused by SARS-CoV-2 was declared a global pandemic by WHO (World Health Organization) in March, 2020. Within 6 months, nearly 750,000 deaths are claimed by COVID-19 across the globe. This called for immediate social, scientific, technological, public and community interventions. Considering the severity of infection and the associated mortalities, global efforts are underway to develop preventive measures against SARS-CoV-2. Among the SARS-CoV-2 target proteins, Spike (S) glycoprotein (a.k.a S Protein) is the most studied target known to trigger strong host immune response. A detailed analysis of S protein-based epitopes enabled us to design a novel B-cell-derived T-cell Multi-epitope-based peptide (MEBP) vaccine candidate. This involved a systematic and comprehensive computational protocol consisting of prediction of dual-purpose epitopes and designing an MEBP vaccine construct. This was followed by 3D structure validation, MEBP complex interaction studies, in silico cloning and vaccine dose-based immune response simulation to evaluate the immunogenic potency of the vaccine construct. The dual-purpose epitope prediction protocol was designed such that the same epitope elicits both humoral and cellular immune response unlike the earlier designs. Further, the epitopes predicted were screened against stringent criteria to ensure selection of a potent candidate with maximum antigen coverage and best immune response. The vaccine dose-based immune response simulation studies revealed a rapid antigen clearance through antibody generation and elevated levels of cell-mediated immunity during repeated exposure of the vaccine. The favourable results of the analysis strongly indicate that the vaccine construct is indeed a potent vaccine candidate and ready to proceed to the next steps of experimental validation and efficacy studies.Supplementary informationThe online version contains supplementary material available at 10.1007/s13205-020-02574-x.
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