Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 679 - 686

Published: Jan. 7, 2022

Abstract The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. first was associated with a mix of lineages, while the second and third waves were driven Beta (B.1.351) Delta (B.1.617.2) variants, respectively 1–3 . In November 2021, genomic surveillance teams South Botswana detected new variant rapid resurgence infections Gauteng province, Africa. Within days genome being uploaded, it designated concern (Omicron, B.1.1.529) World Health Organization and, within weeks, had identified 87 countries. Omicron is exceptional for carrying over 30 mutations spike glycoprotein, which are predicted to influence antibody neutralization function 4 Here we describe profile early transmission dynamics Omicron, highlighting spread regions high levels population immunity.

Language: Английский

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Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(11), P. e1010951 - e1010951

Published: Nov. 18, 2022

SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes impacts of on these biochemical properties, enabling rapid assessment new seen during viral surveillance. However, effects can change as virus evolves, requiring updated deep scans. We determined all single amino acid Omicron BA.1 BA.2 RBDs ACE2-binding affinity, RBD folding, escape from binding by LY-CoV1404 (bebtelovimab) monoclonal antibody. The some differ those measured ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble previously Alpha variant due convergent epistatically modifying N501Y substitution. variants show additional lineage-specific shifts, including examples phenomenon entrenchment causes Q498R substitutions present be more favorable background than earlier strains. In contrast, substitution Q493R exhibits no sign entrenchment, with derived state, R493, being unfavorable for Wuhan-Hu-1. Likely this reason, R493Q reversion has occurred sub-variants BA.4/BA.5 BA.2.75, where affinity buffer may potentiate concurrent antigenic change. Consistent prior studies, we find have reduced expression, identify candidate stabilizing ameliorate deficit. Last, our maps highlight a broadening sites compared datasets landscape inform ongoing efforts

Language: Английский

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The Evolution and Biology of SARS-CoV-2 Variants

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2022, Volume and Issue: 12(5), P. a041390 - a041390

Published: April 20, 2022

Our understanding of the still unfolding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic would have been extremely limited without study genetics and evolution this new human coronavirus. Large-scale genome-sequencing efforts provided close to real-time tracking global spread diversification SARS-CoV-2 since its entry into population in late 2019. These data underpinned analysis origins, epidemiology, adaptations population: principally immune evasion increasing transmissibility. SARS-CoV-2, despite being a pathogen, was highly capable human-to-human transmission. During rapid humans, has evolved independent forms, so-called "variants concern," that are better optimized for The most important adaptation bat progenitor both SARS-CoV-1 infection (and other mammals) is use angiotensin-converting enzyme (ACE2) receptor. Relaxed structural constraints provide plasticity SARS-related spike protein permitting it accommodate significant amino acid replacements antigenic consequence compromising ability bind ACE2. Although bulk research justifiably concentrated on viral as main determinant changes transmissibility, there accumulating evidence contribution regions proteome virus-host interaction. Whereas levels community transmission recombinants genetically distinct variants at present low, when divergent cocirculate, recombination between clades detected, risk viruses with properties emerge. Applying computational machine learning methods genome sequence sets generate experimentally verifiable predictions will serve an early warning system novel variant surveillance be future vaccine planning. Omicron, latest concern, focused attention step change events, "shift," opposed incremental "drift" antigenicity. Both increase transmissibility shift Omicron led readily causing infections fully vaccinated and/or previously infected. Omicron's virulence, while reduced relative concern replaced, Delta, very much premised past exposure individuals clear signal boosted vaccination protects from disease. Currently, proven itself dangerous pathogen unpredictable evolutionary capacity, leading too great not ensure all world screened by sequencing, protected through available affordable vaccines, non-punitive strategies place detecting responding concern.

Language: Английский

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Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 11, 2023

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including R346, K444, L452, N460, F486. Here, we characterize convergent evolution of properties one recent lineage concern, BQ.1.1. Our phylogenetic analysis suggests that these five are recurrently acquired, particularly younger lineages. Epidemic dynamics modelling increase viral fitness, a large proportion fitness variation within lineages can be explained by substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 BA.5 infection sera more efficiently, as demonstrated neutralization assays. The pathogenicity hamsters is lower than BA.5. multiscale investigations illuminate evolutionary rules governing for known 2022.

Language: Английский

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Omicron variant (B.1.1.529) and its sublineages: What do we know so far amid the emergence of recombinant variants of SARS-CoV-2?

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 154, P. 113522 - 113522

Published: Aug. 15, 2022

Since the start of COVID-19 pandemic, numerous variants SARS-CoV-2 have been reported worldwide. The advent concern (VOCs) raises severe concerns amid serious containment efforts against that include physical measures, pharmacological repurposing, immunization, and genomic/community surveillance. Omicron variant (B.1.1.529) has identified as a highly modified, contagious, crucial among five VOCs SARS-CoV-2. increased affinity spike protein (S-protein), host receptor, angiotensin converting enzyme-2 (ACE-2), due to higher number mutations in receptor-binding domain (RBD) S-protein proposed primary reason for decreased efficacy majorly available vaccines transmissible nature variant. Because its significant competitive advantage, sublineages swiftly surpassed other become dominant circulating lineages nations. prevalent strain United Kingdom South Africa. Furthermore, emergence recombinant through conjunction with or by mixing variant's sublineages/subvariants poses major threat humanity. This various issues hazards regarding sublineages, such an breakout susceptible populations fully vaccinated persons. As result, understanding features genetic implications this is crucial. Hence, we explained depth evolution analyzed repercussions on infectiousness, dissemination ability, viral entry mechanism, immune evasion. We also presented viewpoint feasible strategies precluding counteracting any future catastrophic spread omicron could result detrimental wave cases.

Language: Английский

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COVID-19: Challenges of Viral Variants

Annual Review of Medicine, Journal Year: 2022, Volume and Issue: 74(1), P. 31 - 53

Published: July 18, 2022

The COVID-19 pandemic has been accompanied by SARS-CoV-2 evolution and emergence of viral variants that have far exceeded initial expectations. Five major concern (Alpha, Beta, Gamma, Delta, Omicron) emerged, each having both unique overlapping amino acid substitutions affected transmissibility, disease severity, susceptibility to natural or vaccine-induced immune responses monoclonal antibodies. Several the more recent appear evolved properties evasion, particularly in cases prolonged infection. Tracking existing surveillance for new are critical an effective response.

Language: Английский

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Update on the omicron sub‐variants BA.4 and BA.5

Reviews in Medical Virology, Journal Year: 2022, Volume and Issue: 33(1)

Published: Aug. 26, 2022

Abstract Several nations have recently begun to relax their public health protocols, particularly regarding the use of face masks when engaging in outdoor activities. This is because there has been a general trend towards fewer cases coronavirus disease 2019 (COVID‐19). However, new Omicron sub‐variants (designated BA.4 and BA.5) emerged. These two subvariants are thought be cause an increase COVID‐19 South Africa, United States, Europe. They also spread throughout Asia. evolved from lineage with characteristics that make them even more contagious which allow circumvent immunity previous infection or vaccination. article reviews number scientific considerations about these variants, including apparently reduced clinical severity.

Language: Английский

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Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 3, 2023

Abstract Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has documented, direct evidence of subsequent transmission continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 three that led to the emergence, forward transmission, a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), displayed substantial resistance neutralization by sera from boosted and/or BA.1-infected study participants. Subsequent replication resulted (S254F, N448S, F456L, M458K, F981L, S982L) as well five other virus proteins. Our findings demonstrate not only BA.1 lineage can diverge further its already exceptionally mutated genome but also patients with transmit these viral variants. Thus, there is, urgent need implement strategies prevent prolonged limit spread newly emerging, neutralization-resistant variants vulnerable patients.

Language: Английский

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Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 21, 2023

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across world and effectively evaded immune responses, its viral fitness in cell animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent genomes is challenging because length genome (~30 kb). Here, we present a plasmid-based assembly rescue strategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons single ligation reaction with >80% efficiency. Fully sequenced stocks can be generated 1 3 weeks, respectively. By testing series naturally occurring well Delta-Omicron chimeric replicons, show nonstructural protein 6 harbors critical attenuating mutations, which dampen RNA replication reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study reveals deficits function underlying attenuation.

Language: Английский

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Deep-learning-enabled protein–protein interaction analysis for prediction of SARS-CoV-2 infectivity and variant evolution

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(8), P. 2007 - 2018

Published: July 31, 2023

Language: Английский

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