Recurrent SARS-CoV-2 mutations in immunodeficient patients DOI Creative Commons
Samuel Wilkinson,

Alex Richter,

Anna Casey

et al.

Virus Evolution, Journal Year: 2022, Volume and Issue: 8(2)

Published: July 1, 2022

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but understudied. Many case studies have been published which describe one or a small number long-term infected individuals no study has combined these sequences into cohesive dataset. This work aims to rectify this and genomics patient group through combination literature searches as well identifying new series directly from COVID-19 Genomics UK (COG-UK) The spike gene receptor-binding domain N-terminal (NTD) were identified mutation hotspots. Numerous mutations associated with variants concern observed emerge recurrently. Additionally envelope gene, T30I was determined be second most frequent recurrently occurring arising persistent infections. A high proportion recurrent ACE2 affinity, immune escape, viral packaging optimisation. There is apparent selective pressure that aid cell-cell transmission within host persistence often different

Language: Английский

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion DOI Creative Commons
Petra Mlčochová, Steven A. Kemp, Mahesh Shanker Dhar

et al.

Nature, Journal Year: 2021, Volume and Issue: 599(7883), P. 114 - 119

Published: Sept. 6, 2021

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state Maharashtra late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) B.1.1.7 (Alpha)

Language: Английский

Citations

1290
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

1011
The biological and clinical significance of emerging SARS-CoV-2 variants DOI Creative Commons
Kaiming Tao, Philip L. Tzou, Janin Nouhin

et al.

Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 22(12), P. 757 - 773

Published: Sept. 17, 2021

Language: Английский

Citations

991
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

977
Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant DOI Creative Commons
Rigel Suzuki,

Daichi Yamasoba,

Izumi Kimura

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 700 - 705

Published: Feb. 1, 2022

Abstract The emergence of the Omicron variant SARS-CoV-2 is an urgent global health concern 1 . In this study, our statistical modelling suggests that has spread more rapidly than Delta in several countries including South Africa. Cell culture experiments showed to be less fusogenic and ancestral strain SARS-CoV-2. Although spike (S) protein efficiently cleaved into two subunits, which facilitates cell–cell fusion 2,3 , S was compared proteins Furthermore, a hamster model, decreased lung infectivity pathogenic Our multiscale investigations reveal virological characteristics Omicron, rapid growth human population, lower fusogenicity attenuated pathogenicity.

Language: Английский

Citations

629
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
Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation DOI Creative Commons
Akatsuki Saito, Takashi Irie, Rigel Suzuki

et al.

Nature, Journal Year: 2021, Volume and Issue: 602(7896), P. 300 - 306

Published: Nov. 25, 2021

Abstract During the current coronavirus disease 2019 (COVID-19) pandemic, a variety of mutations have accumulated in viral genome severe acute respiratory syndrome 2 (SARS-CoV-2) and, at time writing, four variants concern are considered to be potentially hazardous human society 1 . The recently emerged B.1.617.2/Delta variant is closely associated with COVID-19 surge that occurred India spring 2021 (ref. ). However, virological properties remain unclear. Here we show highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 infected hamsters. P681R mutation spike protein, which conserved this lineage, facilitates cleavage protein enhances fusogenicity. Moreover, demonstrate P681R-bearing virus exhibits higher pathogenicity compared its parental virus. Our data suggest hallmark phenotype enhanced pathogenicity.

Language: Английский

Citations

556
COVID-19 vaccine development: milestones, lessons and prospects DOI Creative Commons
Maochen Li, Han Wang, Lili Tian

et al.

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

Published: May 3, 2022

Abstract With the constantly mutating of SARS-CoV-2 and emergence Variants Concern (VOC), implementation vaccination is critically important. Existing vaccines mainly include inactivated, live attenuated, viral vector, protein subunit, RNA, DNA, virus-like particle (VLP) vaccines. Viral vector vaccines, subunit mRNA may induce additional cellular or humoral immune regulations, including Th cell responses germinal center responses, form relevant memory cells, greatly improving their efficiency. However, some be associated with complications like thrombocytopenia myocarditis, raising concerns about safety these COVID-19 Here, we systemically assess efficacy possible different effects on pregnant women, elderly, people diseases acquired immunodeficiency syndrome (AIDS), transplant recipients, cancer patients. Based current analysis, governments agencies are recommended to continue advance vaccine immunization process. Simultaneously, special attention should paid health status timely treatment complications, development, ensuring lives In addition, available measures such as mix-and-match vaccination, developing new nanoparticle optimizing adjuvant improve could considered.

Language: Английский

Citations

342
Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike DOI Creative Commons

Daichi Yamasoba,

Izumi Kimura,

Hesham Nasser

et al.

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

Citations

315
Rapid assessment of SARS-CoV-2–evolved variants using virus-like particles DOI Creative Commons
Abdullah M. Syed, Taha Y. Taha, Takako Tabata

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6575), P. 1626 - 1632

Published: Dec. 23, 2021

Efforts to determine why new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants demonstrate improved fitness have been limited analyzing mutations in the spike (S) protein with use of S-pseudotyped particles. In this study, we show that SARS-CoV-2 virus-like particles (SC2-VLPs) can package and deliver exogenous transcripts, enabling analysis within all structural proteins at multiple steps viral life cycle. SC2-VLPs, four nucleocapsid (N) found universally more-transmissible independently increased messenger RNA delivery expression ~10-fold, a reverse genetics model, serine-202→arginine (S202R) arginine-203→methionine (R203M) each produced >50 times as much virus. SC2-VLPs provide platform for rapid testing outside biosafety level 3 setting N particle assembly be mechanisms could explain spread variants, including B.1.617.2 (Delta, which contains R203M mutation).

Language: Английский

Citations

300