The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein DOI Creative Commons
Thomas P. Peacock, Jonathan C. Brown, Jie Zhou

et al.

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

Considerable escape of SARS-CoV-2 Omicron to antibody neutralization DOI Open Access
Delphine Planas, Nell Saunders, Piet Maes

et al.

Nature, Journal Year: 2021, Volume and Issue: 602(7898), P. 671 - 675

Published: Dec. 23, 2021

Language: Английский

Citations

1456
Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization DOI Creative Commons
Sandile Cele, Laurelle Jackson, David S. Khoury

et al.

Nature, Journal Year: 2021, Volume and Issue: 602(7898), P. 654 - 656

Published: Dec. 23, 2021

Abstract The emergence of the SARS-CoV-2 variant concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness lead to re-infections 1 . Here we investigated escape from neutralization by antibodies African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination who were previously infected or no evidence previous infection. isolated sequence-confirmed live virus an person observed that requires angiotensin-converting enzyme 2 (ACE2) receptor infect cells. compared plasma relative ancestral strain found was much higher vaccinated-only participants. However, both groups showed a 22-fold reduction vaccine-elicited variant. Participants had been exhibited residual similar level vaccination-only group. These data support notion reasonable protection against be maintained using approaches.

Language: Английский

Citations

1091
SARS-CoV-2 variant biology: immune escape, transmission and fitness DOI Creative Commons
Alessandro M. Carabelli, Thomas P. Peacock, Lucy Thorne

et al.

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

Citations

989
Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity DOI Creative Commons
Bo Meng, Adam Abdullahi, Isabella A. T. M. Ferreira

et al.

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

Citations

976
Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa DOI
Juliet R. C. Pulliam, Cari van Schalkwyk, Nevashan Govender

et al.

Science, Journal Year: 2022, Volume and Issue: 376(6593)

Published: March 15, 2022

We provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes risk and apply these approaches from South Africa's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic date. Although we found no evidence increased associated with circulation the Beta (B.1.351) or Delta (B.1.617.2) variants, did find clear, population-level suggest immune evasion by Omicron (B.1.1.529) variant previously infected individuals Africa. Reinfections occurring between 1 November 2021 31 January 2022 were detected all three previous waves, there has been an increase having a third infection since mid-November 2021.

Language: Английский

Citations

844
Antibody evasion properties of SARS-CoV-2 Omicron sublineages DOI Creative Commons
Sho Iketani, Lihong Liu, Yicheng Guo

et al.

Nature, Journal Year: 2022, Volume and Issue: 604(7906), P. 553 - 556

Published: March 3, 2022

The identification of the Omicron (B.1.1.529.1 or BA.1) variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana November 2021

Language: Английский

Citations

790
The evolution of SARS-CoV-2 DOI Open Access
Peter V. Markov, Mahan Ghafari, Martin Beer

et al.

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

Published: April 5, 2023

Language: Английский

Citations

768
Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study DOI
Nicole Wolter, Waasila Jassat, Sibongile Walaza

et al.

The Lancet, Journal Year: 2022, Volume and Issue: 399(10323), P. 437 - 446

Published: Jan. 1, 2022

Language: Английский

Citations

639
Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa DOI Creative Commons
Houriiyah Tegally, Monika Moir, Josie Everatt

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(9), P. 1785 - 1790

Published: June 27, 2022

Abstract Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant concern predominantly drove South Africa’s fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 BA.5, responsible for a fifth wave infections. The spike proteins BA.5 are identical, similar to except addition 69–70 deletion (present in Alpha BA.1 lineage), L452R Delta variant), F486V wild-type amino acid at Q493. differ only outside region. allows these be by proxy marker S-gene target failure, on background variants not possessing this feature. rapidly replaced BA.2, reaching more than 50% sequenced cases Africa first week April 2022. Using multinomial logistic regression model, we estimated growth advantages 0.08 (95% confidence interval (CI): 0.08–0.09) 0.10 CI: 0.09–0.11) per day, respectively, over Africa. continued discovery genetically diverse points hypothesis that discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing further evolution dispersal virus.

Language: Английский

Citations

609
Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study DOI Creative Commons
Adam S. Lauring, Mark W. Tenforde, James D. Chappell

et al.

BMJ, Journal Year: 2022, Volume and Issue: unknown, P. e069761 - e069761

Published: March 9, 2022

To characterize the clinical severity of covid-19 associated with alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital compare effectiveness mRNA vaccines prevent admissions related each variant.

Language: Английский

Citations

592