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Origin, phylogeny, variability and epitope conservation of SARS-CoV-2 worldwide.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses innumerous challenges, like understanding what triggered the emergence of this new human virus, how this RNA virus is evolving or how the variability of viral genome may impact the primary structure of proteins that are targets for vaccine. We analyzed 19471 SARS-CoV-2 genomes available at the GISAID database from all over the world and 3335 genomes of other Coronoviridae family members available at GenBank, collecting SARS-CoV-2 high-quality genomes and distinct Coronoviridae family genomes. Additionally, we analyzed 199,984 spike glycoprotein sequences. Here, we identify a SARS-CoV-2 emerging cluster containing 13 closely related genomes isolated from bat and pangolin that showed evidence of recombination, which may have contributed to the emergence of SARS-CoV-2. The analyzed SARS-CoV-2 genomes presented 9632 single nucleotide variants (SNVs) corresponding to a variant density of 0.3 over the genome, and a clear geographic distribution. SNVs are unevenly distributed throughout the genome and hotspots for mutations were found for the spike gene and ORF 1ab. We describe a set of predicted spike protein epitopes whose variability is negligible. Additionally, all predicted epitopes for the structural E, M and N proteins are highly conserved. The amino acid changes present in the spike glycoprotein of variables of concern (VOCs) comprise between 3.4% and 20.7% of the predicted epitopes of this protein. These results favors the continuous efficacy of the available vaccines targeting the spike protein, and other structural proteins. Multiple epitopes vaccines should sustain vaccine efficacy since at least some of the epitopes present in variability regions of VOCs are conserved and thus recognizable by antibodies.

SUBMITTER: Vale FF

PROVIDER: S-EPMC8323504 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Variants of concern (VOCs) have been replacing each other during the still rampant COVID-19 pandemic. As a result, SARS-CoV-2 populations have evolved increasingly intricate constellations of mutations that often enhance transmissibility, disease severity, and other epidemiological characteristics. The origin and evolution of these constellations remain puzzling. Methods: Here we study the evolution of VOCs at the proteome level by analyzing about 12 million genomic sequences retrieved from GISAID on July 23, 2022. A total 183,276 mutations were identified and filtered with a relevancy heuristic. The prevalence of haplotypes and free-standing mutations was then tracked monthly in various latitude corridors of the world. Results: A chronology of 22 haplotypes defined three phases driven by protein flexibility-rigidity, environmental sensing, and immune escape. A network of haplotypes illustrated the recruitment and coalescence of mutations into major VOC constellations and seasonal effects of decoupling and loss. Protein interaction networks mediated by haplotypes predicted communications impacting the structure and function of proteins, showing the increasingly central role of molecular interactions involving the spike (S), nucleocapsid (N), and membrane (M) proteins. Haplotype markers either affected fusogenic regions while spreading along the sequence of the S-protein or clustered around binding domains. Modeling of protein structure with AlphaFold2 showed that VOC Omicron and one of its haplotypes were major contributors to the distortion of the M-protein endodomain, which behaves as a receptor of other structural proteins during virion assembly. Remarkably, VOC constellations acted cooperatively to balance the more extreme effects of individual haplotypes. Conclusions: Our study uncovers seasonal patterns of emergence and diversification occurring amid a highly dynamic evolutionary landscape of bursts and waves. The mapping of genetically-linked mutations to structures that sense environmental change with powerful ab initio modeling tools demonstrates the potential of deep-learning for COVID-19 predictive intelligence and therapeutic intervention.

Project description:BackgroundWith limited vaccine supplies, an informed position on the status of SARS-CoV-2 infection in people can assist the prioritization of vaccine deployment.ObjectivesWe performed a systematic review and meta-analysis to estimate the global and regional SARS-CoV-2 seroprevalences around the world.Data sourcesWe systematically searched peer-reviewed databases (PubMed, Embase and Scopus), and preprint servers (medRxiv, bioRxiv and SSRN) for articles published between 1 January 2020 and 30 March 2021.Study eligibility criteriaPopulation-based studies reporting the SARS-CoV-2 seroprevalence in the general population were included.ParticipantsPeople of different age groups, occupations, educational levels, ethnic backgrounds and socio-economic status from the general population.InterventionsThere were no interventions.MethodsWe used the random-eﬀects meta-analyses and empirical Bayesian method to estimate the pooled seroprevalence and conducted subgroup and meta-regression analyses to explore potential sources of heterogeneity as well as the relationship between seroprevalence and socio-demographics.ResultsWe identified 241 eligible studies involving 6.3 million individuals from 60 countries. The global pooled seroprevalence was 9.47% (95% CI 8.99-9.95%), although the heterogeneity among studies was significant (I2 = 99.9%). We estimated that ∼738 million people had been infected with SARS-CoV-2 (as of December 2020). Highest and lowest seroprevalences were recorded in Central and Southern Asia (22.91%, 19.11-26.72%) and Eastern and South-eastern Asia (1.62%, 1.31-1.95%), respectively. Seroprevalence estimates were higher in males, persons aged 20-50 years, in minority ethnic groups living in countries or regions with low income and human development indices.ConclusionsThe present study indicates that the majority of the world's human population was still highly susceptible to SARS-CoV-2 infection in mid-2021, emphasizing the need for vaccine deployment to vulnerable groups of people, particularly in developing countries, and for the implementation of enhanced preventive measures until 'herd immunity' to SARS-CoV-2 has developed.

Project description:The world is experiencing one of the most severe viral outbreaks in the last few years, the pandemic infection by SARS-CoV-2, the causative agent of COVID-19 disease. As of December 10th 2021, the virus has spread worldwide, with a total number of more than 267 million of confirmed cases (four times more in the last year), and more than 5 million deaths. A great effort has been undertaken to molecularly characterize the virus, track the spreading of different variants across the globe with the aim to understand the potential effects in terms of transmission capability and different fatality rates. Here we focus on the genomic diversity and distribution of the virus in the early stages of the pandemic, to better characterize the origin of COVID-19 and to define the geographical and temporal evolution of genetic clades. By performing a comparative analysis of 75401 SARS-CoV-2 reported sequences (as of December 2020), using as reference the first viral sequence reported in Wuhan in December 2019, we described the existence of 26538 genetic variants, the most frequent clustering into four major clades characterized by a specific geographical distribution. Notably, we found the most frequent variant, the previously reported missense p.Asp614Gly in the S protein, as a single mutation in only three patients, whereas in the large majority of cases it occurs in concomitance with three other variants, suggesting a high linkage and that this variant alone might not provide a significant selective advantage to the virus. Moreover, we evaluated the presence and the distribution in our dataset of the mutations characterizing the so called "british variant", identified at the beginning of 2021, and observed that 9 out of 17 are present only in few sequences, but never in linkage with each other, suggesting a synergistic effect in this new viral strain. In summary, this is a large-scale analysis of SARS-CoV-2 deposited sequences, with a particular focus on the geographical and temporal evolution of genetic clades in the early phase of COVID-19 pandemic.

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Origin, phylogeny, variability and epitope conservation of SARS-CoV-2 worldwide.

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