On the origin and evolution of SARS-CoV-2

Experimental & Molecular Medicine, Journal Year: 2021, Volume and Issue: 53(4), P. 537 - 547

Published: April 1, 2021

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global outbreak of a disease (herein referred to as COVID-19). Other viruses in same phylogenetic group have been previous regional outbreaks, including SARS and MERS. SARS-CoV-2 has zoonotic origin, similar causative these outbreaks. repetitive introduction animal into human populations resulting outbreaks suggests that future epidemics are inevitable. Therefore, understanding molecular origin evolution will provide critical insights preparing preventing A key feature its propensity genetic recombination across host species boundaries. Consequently, genome harbors signatures multiple events, likely encompassing broad geographic regions. regions show impact purifying selection. spike (S) protein SARS-CoV-2, which enables virus enter cells, exhibits both selection ancestral leading an effective S capable infecting many other mammalian cells. spread explosive growth population (within hosts) contributed additional mutational variability this genome, increasing opportunities recombination.

Language: Английский

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A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 9, 2022

The infective SARS-CoV-2 is more prone to immune escape. Presently, the significant variants of are emerging in due course time with substantial mutations, having escape property. Simultaneously, vaccination drive against this virus progress worldwide. However, vaccine evasion has been noted by some newly variants. Our review provides an overview variants' and ability. We have illustrated a broad view related viral evolution, variants, Subsequently, different approaches discussed. Different innate strategies adopted discussed like, IFN-I production dysregulation, cytokines escape, associated dendritic cell function macrophages, natural killer cells neutrophils PRRs evasion, NLRP3 inflammasome evasion. Simultaneously we mutations such as RBD region (N439K, L452R, E484K, N501Y, K444R) other parts (D614G, P681R) S-glycoprotein. Mutations locations NSP1, NSP3, NSP6, ORF3, ORF8 also Finally, partial (BioNTech/Pfizer mRNA/Oxford-AstraZeneca/BBIBP-CorV/ZF2001/Moderna mRNA/Johnson & Johnson vaccine) This will help gain in-depth knowledge antibody ability assist controlling current pandemic prepare for next.

Language: Английский

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Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(4), P. e0250780 - e0250780

Published: April 28, 2021

The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control. Such a narrow focus raises specter viral immune evasion as potential failure mode these biomedical interventions. With emergence new strains with altered transmissibility potential, critical question this: how easily can virus escape neutralizing antibodies (nAbs) targeting RBD? To answer this question, we combined an analysis RBD structure-function evolutionary modeling framework. Our revealed that epitopes RBD-targeting nAbs overlap one another substantially be evaded by mutants ACE2 affinities comparable to wild type, are observed in sequence surveillance data infect cells vitro. This suggests fitness cost nAb-evading mutations low. We then used predict frequency before after widespread presence due vaccines, passive immunization or natural immunity. two mildly deleterious expected exist high numbers neutral genetic variation, consequently resistance other rely on protection develop quickly -and repeatedly- positive selection. Predicted timelines those decay kinetics raised against vaccinal antigens, raising second mechanism loss immunity population. Strategies elimination should therefore diversified across targets therapeutic modalities.

Language: Английский

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Molecular Evolution of SARS-CoV-2 during the COVID-19 Pandemic

Genes, Journal Year: 2023, Volume and Issue: 14(2), P. 407 - 407

Published: Feb. 4, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well resistance to monoclonal antibodies polyclonal sera, among other treatments. In order understand causes consequences observed SARS-CoV-2 diversity, a variety studies investigated evolution this virus humans. general, evolves with moderate rate evolution, 10

Language: Английский

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The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins

PLoS Computational Biology, Journal Year: 2021, Volume and Issue: 17(7), P. e1009147 - e1009147

Published: July 8, 2021

The unprecedented pace of the sequencing SARS-CoV-2 virus genomes provides us with unique information about genetic changes in a single pathogen during ongoing pandemic. By analysis close to 200,000 we show that patterns mutations along its genome are closely correlated structural and functional features encoded proteins. Requirements foldability proteins’ 3D structures conservation their key regions, such as protein-protein interaction interfaces, dominant factors driving evolutionary selection protein-coding genes. At same time, avoidance host immunity leads abundance other resulting high variability missense mutation rate genome. “Unexplained” peaks valleys provide hints on function for yet uncharacterized genomic regions specific protein they code for. Some these observations have immediate practical implications target PCR-based COVID-19 tests evaluating risk epitopes targeted by antibodies vaccine design strategies.

Language: Английский

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The Mutation Profile of SARS-CoV-2 Is Primarily Shaped by the Host Antiviral Defense

Viruses, Journal Year: 2021, Volume and Issue: 13(3), P. 394 - 394

Published: March 2, 2021

Understanding SARS-CoV-2 evolution is a fundamental effort in coping with the COVID-19 pandemic. The virus genomes have been broadly evolving due to high number of infected hosts world-wide. Mutagenesis and selection are two inter-dependent mechanisms diversification. However, which contribute mutation profiles remain under-explored. Here, we delineate contribution mutagenesis genome diversity isolates. We generated comprehensive phylogenetic tree representative genomes. Instead counting mutations relative reference genome, identified each event at nodes tree. With this approach, obtained events that independent other profile results suggest heterogeneous patterns mainly reflections host (i) antiviral achieved through APOBEC, ADAR, ZAP proteins, (ii) probable adaptation against reactive oxygen species.

Language: Английский

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Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 17, 2022

Abstract Both T cells and B have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models study one the other are less common. Here, we generate a chimeric protein (SpiN) that comprises receptor binding domain (RBD) from Spike (S) nucleocapsid (N) antigens SARS-CoV-2. Memory CD4 + CD8 specific for SpiN could detected in blood of both individuals vaccinated Coronavac vaccine COVID-19 convalescent donors. In mice, elicited strong IFN-γ response by high levels antibodies inactivated virus, but not detectable neutralizing (nAbs). Importantly, immunization Syrian hamsters human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice Poly ICLC-adjuvanted promotes robust resistance wild type SARS-CoV-2, as indicated viral load, lung inflammation, clinical outcome reduction lethality. The protection induced was ablated depletion transferred mice. Finally, vaccination also protects K18-ACE-2 against Delta Omicron isolates. Hence, formulations elicit effector N RBD proteins may used improve vaccines potentially circumvent immune escape variants concern.

Language: Английский

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Variants in SARS-CoV-2 associated with mild or severe outcome

Evolution Medicine and Public Health, Journal Year: 2021, Volume and Issue: 9(1), P. 267 - 275

Published: Jan. 1, 2021

Abstract Introduction The coronavirus disease 2019 (COVID-19) pandemic is a global public health emergency causing disparate burden of death and disability around the world. viral genetic variants associated with outcome severity are still being discovered. Methods We downloaded 155 958 severe acute respiratory syndrome 2 (SARS-CoV-2) genomes from GISAID. Of these genomes, 3637 samples included useable metadata on patient outcomes. Using this subset, we evaluated whether SARS-CoV-2 genomic improved prediction reported beyond age region. First, established including as model features meaningfully increased predictive power our model. Next, specific in order to determine magnitude association frequency among genomes. Results Logistic regression models that outperformed other (area under curve = 0.91 compared 0.68 for gender alone; P < 0.001). found 84 odds ratios greater than (17 67 higher lower severity, respectively). median was 0.15% (interquartile range 0.09–0.45%). Altogether 85% had at least one variant outcome. Conclusion Numerous have 2-fold or mild collectively, common. In addition comprehensive mitigation efforts, measures should be prioritized control more manifestations COVID-19 transmission chains linked cases. Lay summary: This study explores which, if any, Our results suggest there common often negative outcomes, which may impact downstream measures.

Language: Английский

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Natural Selection Plays an Important Role in Shaping the Codon Usage of Structural Genes of the Viruses Belonging to the Coronaviridae Family

Viruses, Journal Year: 2020, Volume and Issue: 13(1), P. 3 - 3

Published: Dec. 22, 2020

Viruses belonging to the Coronaviridae family have a single-stranded positive-sense RNA with poly-A tail. The genome has length of ~29.9 kbps, which encodes for genes that are essential cell survival and replication. Different evolutionary constraints constantly influence codon usage bias (CUB) different genes. A virus optimizes its fit host environment on it savors. This study is comprehensive analysis CUB encoded by viruses family. methods including relative synonymous (RSCU), an Effective number codons (ENc), parity plot 2, Neutrality plot, were adopted analyze factors responsible genetic evolution Base composition RSCU analyses demonstrated presence A-ended U-ended being preferred in 3rd position suggestive mutational selection. lesser ENc value spike ‘S’ gene suggests higher this compared other structural Parity 2 neutrality demonstrate role extent natural selection towards pattern. It was observed analyzed at least under 84% selection, implying major shaping usage.

Language: Английский

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Risk of evolutionary escape from neutralizing antibodies targeting SARS-CoV-2 spike protein

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: Nov. 20, 2020

Abstract As many prophylactics targeting SARS-CoV-2 are aimed at the spike protein receptor-binding domain (RBD), we examined risk of immune evasion from previously published RBD-targeting neutralizing antibodies (nAbs). Epitopes for nAbs overlap one another substantially and can give rise to escape mutants with ACE2 affinities comparable wild type that still infect cells in vitro . We used evolutionary modeling predict frequency before after widespread presence due vaccines, passive immunization or natural immunity. Our suggests two mildly deleterious mutations expected exist high numbers neutral genetic variation, consequently resistance single double antibody combinations develop quickly under positive selection. One Sentence Summary will evolve evade widely deployed monoclonal antibodies, requiring rely on least three distinct epitopes suppress viral evasion.

Language: Английский

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