An interactive viral genome evolution network analysis system enabling rapid large-scale molecular tracing of SARS-CoV-2.
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ABSTRACT:
SUBMITTER: Ling Y
PROVIDER: S-EPMC8743795 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Coronavirus disease 2019 (COVID-19) is an evolving global public health crisis in need of therapeutic options. Passive immunization of monoclonal antibodies (mAbs) represents a promising therapeutic strategy capable of conferring immediate protection from SARS-CoV-2 infection. Herein, we describe the discovery and characterization of neutralizing SARS-CoV-2 IgG and VHH antibodies from four large-scale phage libraries. Each library was constructed synthetically with shuffled complementarity-determining region loops from natural llama and human antibody repertoires. While most candidates targeted the receptor-binding domain of the S1 subunit of SARS-CoV-2 spike protein, we also identified a neutralizing IgG candidate that binds a unique epitope on the N-terminal domain. A select number of antibodies retained binding to SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa and Delta. Overall, our data show that synthetic phage libraries can rapidly yield SARS-CoV-2 S1 antibodies with therapeutically desirable features, including high affinity, unique binding sites, and potent neutralizing activity in vitro, and a capacity to limit disease in vivo.
| S-EPMC8726723 | biostudies-literature
Project description:ObjectiveTo systematically review evidence on effectiveness of contact tracing apps (CTAs) for SARS-CoV-2 on epidemiological and clinical outcomes.DesignRapid systematic review.Data sourcesEMBASE (OVID), MEDLINE (PubMed), BioRxiv and MedRxiv were searched up to 28 October 2020.Study selectionStudies, both empirical and model-based, assessing effect of CTAs for SARS-CoV-2 on reproduction number (R), total number of infections, hospitalisation rate, mortality rate, and other epidemiologically and clinically relevant outcomes, were eligible for inclusion.Data extractionEmpirical and model-based studies were critically appraised using separate checklists. Data on type of study (ie, empirical or model-based), sample size, (simulated) time horizon, study population, CTA type (and associated interventions), comparator and outcomes assessed, were extracted. The most important findings were extracted and narratively summarised. Specifically for model-based studies, characteristics and values of important model parameters were collected.Results2140 studies were identified, of which 17 studies (2 empirical, 15 model-based studies) were eligible and included in this review. Both empirical studies were observational (non-randomised) studies and at high risk of bias, most importantly due to risk of confounding. Risk of bias of model-based studies was considered low for 12 out of 15 studies. Most studies demonstrated beneficial effects of CTAs on R, total number of infections and mortality rate. No studies assessed effect on hospitalisation. Effect size was dependent on model parameters values used, but in general, a beneficial effect was observed at CTA adoption rates of 20% or higher.ConclusionsCTAs have the potential to be effective in reducing SARS-CoV-2 related epidemiological and clinical outcomes, though effect size depends on other model parameters (eg, proportion of asymptomatic individuals, or testing delays), and interventions after CTA notification. Methodologically sound comparative empirical studies on effectiveness of CTAs are required to confirm findings from model-based studies.
| S-EPMC8277487 | biostudies-literature
Project description:ObjectivesStudies are needed to better understand the genomic evolution of the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to describe genomic diversity of SARS-CoV-2 by next-generation sequencing (NGS) in a patient with longitudinal follow-up for SARS-CoV-2 infection.MethodsSequential samples collected between January 29th and February 4th, 2020, from a patient infected by SARS-CoV-2 were used to perform amplification of two genome fragments-including genes encoding spike, envelope, membrane and nucleocapsid proteins-and NGS was carried out with Illumina® technology. Phylogenetic analysis was performed with PhyML and viral variant identification with VarScan.ResultsMajority consensus sequences were identical in most of the samples (5/7) and differed in one synonymous mutation from the Wuhan reference sequence. We identified 233 variants; each sample harboured in median 38 different minority variants, and only four were shared by different samples. The frequency of mutation was similar between genes and correlated with the length of the gene (r = 0.93, p = 0.0002). Most of mutations were substitution variations (n = 217, 93.1%) and about 50% had moderate or high impact on gene expression. Viral variants also differed between lower and upper respiratory tract samples collected on the same day, suggesting independent sites of replication of SARS-CoV-2.ConclusionsWe report for the first time minority viral populations representing up to 1% during the course of SARS-CoV-2 infection. Quasispecies were different from one day to the next, as well as between anatomical sites, suggesting that in vivo this new coronavirus appears as a complex and dynamic distributions of variants.
| S-EPMC7378485 | biostudies-literature
Project description:SARS-CoV-2 (SARS2) infection of a novel permissive host species can result in rapid viral evolution. Data suggest that felids are highly susceptible to SARS2 infection, and species-specific adaptation following human-to-felid transmission may occur. We employed experimental infection and analysis of publicly available SARS2 sequences to observe variant emergence and selection in domestic cats. Three cohorts of cats (N = 23) were inoculated with SARS-CoV-2 USA-WA1/2020 or infected via cat-to-cat contact transmission. Full viral genomes were recovered from RNA obtained from nasal washes 1-3 days post-infection and analyzed for within-host viral variants. We detected 118 unique variants at ≥3 per cent allele frequency in two technical replicates. Seventy of these (59 per cent) were nonsynonymous single nucleotide variants (SNVs); the remainder were synonymous SNVs or structural variants. On average, we observed twelve variants per cat, nearly 10-fold higher than what is commonly reported in human patients. We observed signatures of positive selection in the spike protein and the emergence of eleven within-host variants located at the same genomic positions as mutations in SARS2 variant lineages that have emerged during the pandemic. Fewer variants were noted in cats infected from contact with other cats and in cats exposed to lower doses of cultured inoculum. An analysis of ninety-three publicly available SARS2 consensus genomes recovered from naturally infected domestic cats reflected variant lineages circulating in the local human population at the time of sampling, illustrating that cats are susceptible to SARS2 variants that have emerged in humans, and suggesting human-to-felid transmission occurring in domestic settings is typically unidirectional. These experimental results underscore the rapidity of SARS2 adaptation in felid hosts, representing a theoretical potential origin for variant lineages in human populations. Further, cats should be considered susceptible hosts capable of shedding virus during infections occurring within households.
| S-EPMC9619536 | biostudies-literature
Project description:The race between pathogens and their hosts is a major evolutionary driver, where both reshuffle their genomes to overcome and reorganize the defenses for infection, respectively. Evolutionary theory helps formulate predictions on the future evolutionary dynamics of SARS-CoV-2, which can be monitored through unprecedented real-time tracking of SARS-CoV-2 population genomics at the global scale. Here we quantify the accelerating evolution of SARS-CoV-2 by tracking the SARS-CoV-2 mutation globally, with a focus on the Receptor Binding Domain (RBD) of the spike protein determining infection success. We estimate that the > 820 million people that had been infected by October 5, 2021, produced up to 1021 copies of the virus, with 12 new effective RBD variants appearing, on average, daily. Doubling of the number of RBD variants every 89 days, followed by selection of the most infective variants challenges our defenses and calls for a shift to anticipatory, rather than reactive tactics involving collaborative global sequencing and vaccination.
| S-EPMC9017738 | biostudies-literature
Project description:BackgroundMost patients with SARS-CoV-2 are non-infectious within 2 weeks, though viral RNA may remain detectable for weeks. However there are reports of persistent SARS-CoV-2 infection, with viable virus and ongoing infectivity months after initial detection. Beyond individuals, viral evolution during persistent infections may be accelerated, driving emergence of mutations associated with viral variants of concern. These patients often do not meet inclusion criteria for clinical trials, meaning clinical and virologic characteristics, and optimal management strategies are poorly evidence-based.MethodsWe analysed cases of SARS-CoV-2 infection from a regional testing laboratory in South-West England between March 2020 and December 2021, with at least two SARS-CoV-2 positive samples separated by ≥ 56 days were identified. Excluding those with confirmed or likely re-infection, we identified patients with persistent infection, characterised by an ongoing clinical syndrome consistent with COVID-19 alongside monophyletic viral lineage of SARS-CoV-2. We examined clinical and virologic characteristics, treatment, and outcome. We further performed a literature review investigating cases of persistent SARS-CoV-2 infection, reviewing patient characteristics and treatment.ResultsWe identified six patients with persistent SARS-CoV-2 infection. All were hypogammaglobulinaemic and had underlying haematological malignancy, with four having received B-cell depleting therapy. Evidence of viral evolution, including accrual of mutations associated with variants of concern, was demonstrated in five cases. Four patients ultimately cleared SARS-CoV-2. In two patients, clearance followed treatment with casirivimab/imdevimab. Both survived beyond thirty days following viral clearance, having experienced infections of 305- and 269-days duration respectively, after failed attempts at clearance with alternative therapies. We found 60 cases of confirmed persistent infection in the literature, with a further 31 probable cases. Of those, 80% of patients treated with monoclonal antibodies cleared SARS-CoV-2, and none died.ConclusionHaematological malignancy and patients receiving B-cell depleting therapies represent key groups at risk of persistent SARS-CoV-2 infection. Throughout persistent infection, SARS-CoV-2 can evolve rapidly, giving rise to significant mutations, including those implicated in variants of concern. Monoclonal antibodies appear to be a promising therapeutic option, potentially in combination with antivirals, crucial for individuals, and for public health.
| S-EPMC9666269 | biostudies-literature
Project description:Over the past several decades, we have argued that cultural evolution can facilitate the evolution of large-scale cooperation because it often leads to more rapid adaptation than genetic evolution, and, when multiple stable equilibria exist, rapid adaptation leads to variation among groups. Recently, Lehmann, Feldman, and colleagues have published several papers questioning this argument. They analyze models showing that cultural evolution can actually reduce the range of conditions under which cooperation can evolve and interpret these models as indicating that we were wrong to conclude that culture facilitated the evolution of human cooperation. In the main, their models assume that rates of cultural adaption are not strong enough compared to migration to maintain persistent variation among groups when payoffs create multiple stable equilibria. We show that Lehmann et al. reach different conclusions because they have made different assumptions. We argue that the assumptions that underlie our models are more consistent with the empirical data on large-scale cultural variation in humans than those of Lehmann et al., and thus, our models provide a more plausible account of the cultural evolution of human cooperation in large groups. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00265-010-1100-3) contains supplementary material, which is available to authorized users.
| S-EPMC3038225 | biostudies-literature
Project description:A variety of extremely challenging biological sequence analyses were conducted on the XSEDE large shared memory resource Blacklight, using current bioinformatics tools and encompassing a wide range of scientific applications. These include genomic sequence assembly, very large metagenomic sequence assembly, transcriptome assembly, and sequencing error correction. The data sets used in these analyses included uncategorized fungal species, reference microbial data, very large soil and human gut microbiome sequence data, and primate transcriptomes, composed of both short-read and long-read sequence data. A new parallel command execution program was developed on the Blacklight resource to handle some of these analyses. These results, initially reported previously at XSEDE13 and expanded here, represent significant advances for their respective scientific communities. The breadth and depth of the results achieved demonstrate the ease of use, versatility, and unique capabilities of the Blacklight XSEDE resource for scientific analysis of genomic and transcriptomic sequence data, and the power of these resources, together with XSEDE support, in meeting the most challenging scientific problems.
| S-EPMC4185199 | biostudies-other
Project description:Vaccination against SARS-CoV-2 has greatly mitigated the impact of the COVID-19 pandemic. However, concerns have been raised about the degree to which vaccination might drive the emergence and selection of immune escape mutations that will hamper the efficacy of the vaccines. In this study, we investigate whether vaccination impacted the micro-scale adaptive evolution of SARS-CoV-2 in the Oslo region of Norway, during the first nine months of 2021, a period in which the population went from near-zero to almost 90 per cent vaccine coverage in the population over 50 years old. Weekly aggregated data stratified by age on vaccine uptake and number of SARS-CoV-2 cases in the area were obtained from the National Immunization Registry and the Norwegian Surveillance System for Communicable Diseases, respectively. A total of 6,438 virus sequences (7.5 per cent of the registered cases) along with metadata were available. We used a causal-driven approach to investigate the relationship between vaccination progress and changes in the frequency of 362 mutations present in at least ten samples, conditioned on the emergence of new lineages, time, and population vaccination coverage. After validating our approach, we identified 21 positive and 12 negative connections between vaccination progress and mutation prevalence, and most of them were outside the Spike protein. We observed a tendency for the mutations that we identified as positively connected with vaccination to decrease as the vaccinated population increased. After modelling the fitness of different competing mutations in a population, we found that our observations could be explained by a clonal interference phenomenon in which high fitness mutations would be outcompeted by the emergence or introduction of other high-fitness mutations.
| S-EPMC10776306 | biostudies-literature
Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for the coronavirus disease 2019 (COVID-19). The high rate of mutation of this virus is associated with a quick emergence of new viral variants that have been rapidly spreading worldwide. Several mutations have been documented in the receptor-binding domain (RBD) of the viral spike protein that increases the interaction between SARS-CoV-2 and its cellular receptor, the angiotensin-converting enzyme 2 (ACE2). Mutations in the spike can increase the viral spread rate, disease severity, and the ability of the virus to evade either the immune protective responses, monoclonal antibody treatments, or the efficacy of current licensed vaccines. This review aimed to highlight the functional virus classification used by the World Health Organization (WHO), Phylogenetic Assignment of Named Global Outbreak (PANGO), Global Initiative on Sharing All Influenza Data (GISAID), and Nextstrain, an open-source project to harness the scientific and public health potential of pathogen genome data, the chronological emergence of viral variants of concern (VOCs) and variants of interest (VOIs), the major findings related to the rate of spread, and the mutations in the spike protein that are involved in the evasion of the host immune responses elicited by prior SARS-CoV-2 infections and by the protection induced by vaccination.
| S-EPMC9025907 | biostudies-literature