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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Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 706 - 714

Published: Feb. 1, 2022

Abstract The SARS-CoV-2 Omicron BA.1 variant emerged in 2021 1 and has multiple mutations its spike protein 2 . Here we show that the of a higher affinity for ACE2 compared with Delta, marked change antigenicity increases Omicron’s evasion therapeutic monoclonal vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as third vaccine dose rescues broadens neutralization. Importantly, antiviral drugs remdesivir molnupiravir retain efficacy against BA.1. Replication was similar Delta virus isolates human nasal epithelial cultures. However, lung cells gut cells, demonstrated lower replication. less efficiently cleaved Delta. differences replication were mapped to entry efficiency on basis spike-pseudotyped assays. defect pseudotyped specific cell types effectively correlated cellular RNA expression TMPRSS2 , deletion affected greater extent than Omicron. Furthermore, drug inhibitors targeting pathways 3 inefficiently uses protease TMPRSS2, which promotes through plasma membrane fusion, dependency endocytic pathway. Consistent suboptimal S1/S2 cleavage inability use syncytium formation by substantially impaired spike. efficient at is associated shift tropism away from TMPRSS2-expressing implications altered pathogenesis.

Language: Английский

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The evolution of SARS-CoV-2

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(6), P. 361 - 379

Published: April 5, 2023

Language: Английский

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SARS-CoV-2 Omicron variant: recent progress and future perspectives

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

Published: April 28, 2022

Abstract Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there have been a few variants severe acute respiratory syndrome 2 (SARS-CoV-2), one which is Omicron variant (B.1.1.529). The most mutated SARS-CoV-2 variant, and its high transmissibility immune evasion ability raised global concerns. Owing to enhanced transmissibility, has rapidly replaced Delta as dominant in several regions. However, recent studies shown that exhibits reduced pathogenicity due altered cell tropism. In addition, significant resistance neutralizing activity vaccines, convalescent serum, antibody therapies. present review, advances molecular clinical characteristics infectivity, pathogenicity, was summarized, potential therapeutic applications response infection were discussed. Furthermore, we highlighted future waves strategies end pandemic.

Language: Английский

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Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike

Cell, Journal Year: 2022, Volume and Issue: 185(12), P. 2103 - 2115.e19

Published: May 2, 2022

Soon after the emergence and global spread of SARS-CoV-2 Omicron lineage BA.1, another lineage, BA.2, began outcompeting BA.1. The results statistical analysis showed that effective reproduction number BA.2 is 1.4-fold higher than Neutralization experiments revealed immunity induced by COVID vaccines widely administered to human populations not against similar antigenicity notably different from Cell culture spike confers replication efficacy in nasal epithelial cells more efficient mediating syncytia formation BA.1 spike. Furthermore, infection using hamsters indicated spike-bearing virus pathogenic virus. Altogether, our multiscale investigations suggest risk health potentially

Language: Английский

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Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

Environmental Research, Journal Year: 2022, Volume and Issue: 209, P. 112816 - 112816

Published: Jan. 29, 2022

Language: Английский

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The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 3, 2022

Abstract The SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, Omicron/BA.2 early 2022. Here, we describe how Omicron BA.1 BA.2 show a lower severity phenotype hamster model of pathogenicity which maps specifically to spike gene. We further that is attenuated lung cell line but replicates more rapidly, albeit peak titres, human primary nasal cells. This replication also (including emerging BA.4) shows fusogenicity preference for entry via endosomal route. map altered route partially S2 domain, particularly substitution N969K. Finally, pseudovirus with spike, engineered domain confer Delta-like retains antigenic properties Omicron. distinct separation between genetic determinants these two key phenotypes, raising concerning possibility future variants large distance from currently circulating vaccine strains will not necessarily display intrinsic seen during infection.

Language: Английский

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Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2

Nature, Journal Year: 2022, Volume and Issue: 607(7917), P. 119 - 127

Published: May 16, 2022

Language: Английский

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Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 31(1), P. 9 - 17.e3

Published: Nov. 22, 2022

Language: Английский

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A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 167 - 167

Published: Jan. 5, 2023

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all previously emerged variants. numerous mutations in Omicron’s viral genome sub-lineages attribute it a larger amount of fitness, owing to alteration transmission pathophysiology virus. With rapid change structure, sub-variants, namely BA.1, BA.2, BA.3, BA.4, BA.5, dominate community with an ability escape neutralization efficiency induced prior vaccination or infections. Similarly, several recombinant sub-variants Omicron, XBB, XBD, XBF, etc., have emerged, which better understanding. This review mainly entails changes due having higher number mutations. binding affinity, cellular entry, disease severity, infection rates, importantly, immune evading potential them discussed this review. A comparative analysis Delta other variants evolved before gives readers in-depth understanding landscape infection. Furthermore, discusses range abilities possessed approved antiviral therapeutic molecules neutralizing antibodies functional against sub-variants. evolution is causing infections, but broader aspect their not been explored. Thus, scientific should adopt elucidative approach obtain clear idea about recently including variants, so effective vaccines drugs can be achieved. This, turn, will lead drop cases and, finally, end pandemic.

Language: Английский

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