SARS-CoV-2 variant biology: immune escape, transmission and fitness

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Language: Английский

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Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness

Science, Journal Year: 2022, Volume and Issue: 376(6599), P. 1327 - 1332

Published: May 24, 2022

Repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased fitness underscores the value rapid detection and characterization new lineages. We have developed PyR 0 , a hierarchical Bayesian multinomial logistic regression model that infers relative prevalence all viral lineages across geographic regions, detects increasing in prevalence, identifies mutations relevant to fitness. Applying publicly available SARS-CoV-2 genomes, we identify numerous substitutions increase fitness, including previously identified spike many nonspike within nucleocapsid nonstructural proteins. forecasts growth from their mutational profile, ranks as sequences become available, prioritizes biological public health concern for functional characterization.

Language: Английский

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SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 872 - 880.e3

Published: Jan. 20, 2022

Although infections among vaccinated individuals lead to milder COVID-19 symptoms relative those in unvaccinated subjects, the specificity and durability of antibody responses elicited by breakthrough cases remain unknown. Here, we demonstrate that induce serum-binding -neutralizing are markedly more potent, durable, resilient spike mutations observed variants than subjects who received only 2 doses vaccine. However, show cases, were after infection, three times have serum-neutralizing activity comparable magnitude breadth, indicating an increased number exposures SARS-CoV-2 antigen(s) enhance quality responses. Neutralization SARS-CoV was moderate, however, underscoring importance developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.

Language: Английский

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Omicron mutations enhance infectivity and reduce antibody neutralization of SARS-CoV-2 virus-like particles

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(31)

Published: July 19, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant contains extensive sequence changes relative to the earlier-arising B.1, B.1.1, and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity response existing vaccines. Using virus-like particles (VLPs), we examined mutations in all four structural proteins found showed 4.6-fold higher luciferase delivery overall ancestral B.1 lineage, a property conferred mostly by enhancements S N proteins, while M E were detrimental assembly. Thirty-eight antisera samples from individuals vaccinated with Pfizer/BioNTech, Moderna, or Johnson & vaccines convalescent sera unvaccinated COVID-19 survivors had 15-fold lower efficacy prevent cell transduction VLPs containing spike protein. A third dose of Pfizer vaccine elicited substantially neutralization titers against Omicron, resulting detectable neutralizing antibodies eight out subjects compared one preboosting. Furthermore, monoclonal antibody therapeutics casirivimab imdevimab robust activity but no VLPs, newly authorized bebtelovimab maintained across variants. Our results suggest has similar assembly efficiency entry its rapid spread is due reduced previously subjects. In addition, most currently available will not be useful treating Omicron-infected patients exception bebtelovimab.

Language: Английский

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Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

Cell, Journal Year: 2022, Volume and Issue: 185(9), P. 1539 - 1548.e5

Published: March 18, 2022

Language: Английский

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The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics

Virology Journal, Journal Year: 2023, Volume and Issue: 20(1)

Published: Jan. 10, 2023

Coronavirus disease 2019 (COVID-19) continues to take a heavy toll on personal health, healthcare systems, and economies around the globe. Scientists are expending tremendous effort develop diagnostic technologies for detecting positive infections within shortest possible time, vaccines drugs specifically prevention treatment of COVID-19 disease. At same emerging novel variants have raised serious concerns about vaccine efficacy. The SARS-CoV-2 nucleocapsid (N) protein plays an important role in coronavirus life cycle, participates various vital activities after virus invasion. It has attracted large amount attention drug development. Here, we summarize latest research N protein, including its structure function, post-translational modifications addition involvement liquid-liquid phase separation (LLPS) use as basis development techniques.

Language: Английский

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SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

EBioMedicine, Journal Year: 2022, Volume and Issue: 84, P. 104270 - 104270

Published: Sept. 18, 2022

BackgroundGenetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. The introduction global vaccine programs has contributed to lower COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, Omicron BA.1 emerged, with substantially altered genetic differences clinical effects from other concern. Shortly after dominating spread early 2022, was supplanted by the genetically lineage BA.2. A sub-lineage BA.2, designated BA.5, presently an outgrowth advantage over BA.2 sub-lineages. Here we study neutralisation BA.1, BA.5 pre-Omicron using a range convalescent sera therapeutic monoclonal antibodies live virus assay. Using primary nasopharyngeal swabs, also tested relative fitness compared lineages their ability use ACE2-TMPRSS2 pathway.MethodsUsing low passage isolates Clade A.2.2, Beta, Delta, determined humoral vitro vaccinated cohorts, concentrated human IgG pooled thousands plasma donors, licensed antibody therapies. We then infectivity particle ratios samples expanded engineered ACE2/TMPRSS2 cell line presence absence TMPRSS2 inhibitor Nafamostat.FindingsPeak responses 3 doses BNT162b2 were associated 9-fold reduction for BA.5. Concentrated donors vaccination breakthrough infections greater breadth neutralisation, although potency still reduced 7-fold across all lineages. Testing grade revealed 14.3-fold Evusheld 16.8-fold Sotrovimab Whilst attenuated entry, observed be equivalent that 2020 circulating clade had sensitivity Nafamostat.InterpretationObservations support significantly escape neutralising and/or responses. Potency is differs key difference sub-variants reversion tropism back well-known pathway, utilised efficiently Monitoring if these changes influence transmission disease severity will ongoing tracking management waves globally.FundingThis work primarily supported Australian Medical Foundation research grants MRF2005760 (ST, GM & WDR), MRF2001684 (ADK ST) Research Future Fund Antiviral Development Call grant (WDR), (MRFF2001684, ADK SGT) New South Wales Health Grants Round (SGT).

Language: Английский

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Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 28, 2022

Abstract The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of virus genome. consistently emerging SARS-CoV-2 variants harboring critical mutations impact molecular characteristics viral proteins display heterogeneous behaviors in immune evasion, transmissibility, clinical manifestation during infection, which differ each strain endow them with distinguished features populational spread. Several variants, identified as Variants Concern (VOC) World Health Organization, challenged efforts on control due rapid worldwide spread enhanced evasion from current antibodies vaccines. Moreover, recent Omicron variant even exacerbated anxiety continuous pandemic. Its significant medical treatment disease highlights necessity combinatory investigation mutational pattern influence dynamics against immunity, would greatly facilitate drug vaccine development benefit policymaking. Hence this review, we summarized characteristics, impacts focused parallel comparison different profile, transmissibility tropism alteration, effectiveness, manifestations, order provide a comprehensive landscape for research.

Language: Английский

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Context-specific emergence and growth of the SARS-CoV-2 Delta variant

Nature, Journal Year: 2022, Volume and Issue: 610(7930), P. 154 - 160

Published: Aug. 11, 2022

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences COVID-19 worldwide1,2. emergence the in UK occurred on background a heterogeneous landscape immunity and relaxation non-pharmaceutical interventions. Here we analyse 52,992 genomes from England together with 93,649 rest world to reconstruct quantify its introduction regional dissemination across context changing travel social restrictions. Using analysis human movement, contact tracing virus genomic data, find that geographic focus expansion shifted India more global pattern early May 2021. In England, lineages were introduced than 1,000 times nationally as interventions relaxed. We hotel quarantine for travellers reduced onward transmission importations; however, chains later dominated wave seeded before restrictions introduced. Increasing inter-regional within drove nationwide Delta, some cities receiving 2,000 observable introductions elsewhere. Subsequently, increased levels local population mixing-and not number importations-were associated faster relative Delta. invasion dynamics depended spatial heterogeneity patterns, our findings will inform optimal reduce current future variants concern, such Omicron B.1.1.529).

Language: Английский

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Neuropilin-1 Mediates SARS-CoV-2 Infection of Astrocytes in Brain Organoids, Inducing Inflammation Leading to Dysfunction and Death of Neurons

mBio, Journal Year: 2022, Volume and Issue: 13(6)

Published: Oct. 31, 2022

Coronavirus disease 2019 (COVID-19) is frequently associated with neurological deficits, but how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces these effects remains unclear. Here, we show that astrocytes are readily infected by SARS-CoV-2, surprisingly, neuropilin-1, not angiotensin-converting enzyme (ACE2), serves as the principal receptor mediating cell entry. Infection further positively modulated two-pore segment channel (TPC2) protein regulates membrane trafficking and endocytosis. Astrocyte infection produces a pathological response closely resembling reactive astrogliosis characterized elevated type I interferon (IFN) production, increased inflammation, decreased expression of transporters water, ions, choline, neurotransmitters. These combined events initiated within produce hostile microenvironment promotes dysfunction death uninfected bystander neurons.

Language: Английский

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