TMPRSS2 activation of Omicron lineage Spike glycoprotein is regulated by Collectrin-like domain of ACE2 DOI Creative Commons
Anupriya Aggarwal, Christina Fichter, Vanessa Milogiannakis

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 22, 2023

Abstract Continued high-level spread of SARS-CoV-2 has enabled an accumulation changes within the Spike glycoprotein, leading to resistance neutralising antibodies and concomitant entry requirements that increased viral transmission fitness. Herein, we demonstrate a significant change in angiotensin-converting enzyme 2 (ACE2) transmembrane serine protease (TMPRSS2) dependent by primary isolates occurred upon arrival Omicron lineages. Mechanistically show this shift be function two distinct ACE2 pools based on TMPRS22 association with Collectrin-Like Domain (CLD). In engineered cells overexpressing TMPRSS2, ACE2/TMPRSS2 complexes led either augmentation or attenuation infectivity pre-Omicron lineages, respectively. Mutagenesis ACE2-CLD TMPRSS2 cleavage site restored across all lineages through enabling binding facilitated activation fusion. Our data supports evolution towards use unable form consistent structure as chaperone for many tissue specific amino acid transport proteins. Graphical Abstract: ACE2-TMPRSS2 pool model tropism. A. &-B. reconcile evolving tropism vivo . Both SARS-CoV-1 early (pre-Omicron) have molecular dual tropism, efficient when (blue protein) can (green settings where is excluded from (C4-ACE2 CLD). both initially engages spike fusion then triggered S2 domain B. Over time, (with without TMPRSS2) been lost, consolidation no longer complex. With could enable fusogenic (TMPRSS2 “off” confirmation”). Rather, only uncoupled facilitate latter S2. C. time further consolidated over generations omicron 2022 (BA.1, BA.2 BA.5) 2023 (XBB.1.5) now 2024 JN.1 such KP.3. Overall, initial clades similar observed SARS-CoV-1, replication proceeding tissues would prevalent (e.g. Lung). The away structurally solute carriers SLCA619 SLCA620) selection manner sustained fitness human population.

Language: Английский

Severity and outcomes of Omicron variant of SARS-CoV-2 compared to Delta variant and severity of Omicron sublineages: a systematic review and metanalysis DOI Creative Commons
Pryanka Relan, Nkengafac Villyen Motaze, Kavita Kothari

et al.

BMJ Global Health, Journal Year: 2023, Volume and Issue: 8(7), P. e012328 - e012328

Published: July 1, 2023

Objectives To compare severity and clinical outcomes from Omicron as compared with the Delta variant to between sublineages. Methods We searched WHO COVID-19 Research database for studies that patients variant, separately sublineages BA.1 BA.2. A random-effects meta-analysis was used pool estimates of relative risk (RR) variants Heterogeneity assessed using I 2 index. Risk bias tool developed by Clinical Advances through Information Translation team. Results Our search identified 1494 42 met inclusion criteria. Eleven were published preprints. Of studies, 29 adjusted vaccination status; 12 had no adjustment; 1, adjustment unclear. Three included versus As Delta, individuals infected 61% lower death (RR 0.39, 95% CI 0.33 0.46) 56% hospitalisation 0.44, 0.34 0.56). similarly associated intensive care unit (ICU) admission, oxygen therapy, non-invasive invasive ventilation. The pooled ratio outcome when comparing BA.2 0.55 (95% 0.23 1.30). Discussion hospitalisation, ICU ventilation Delta. There difference in PROSPERO registration number CRD42022310880.

Language: Английский

Citations

57
Rapid review and meta-analysis of serial intervals for SARS-CoV-2 Delta and Omicron variants DOI Creative Commons
Zachary J. Madewell, Yang Yang, Ira M. Longini

et al.

BMC Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(1)

Published: June 26, 2023

The serial interval is the period of time between symptom onset in primary case and secondary case. Understanding important for determining transmission dynamics infectious diseases like COVID-19, including reproduction number attack rates, which could influence control measures. Early meta-analyses COVID-19 reported intervals 5.2 days (95% CI: 4.9-5.5) original wild-type variant 4.87-5.47) Alpha variant. has been shown to decrease over course an epidemic other respiratory diseases, may be due accumulating viral mutations implementation more effective nonpharmaceutical interventions. We therefore aggregated literature estimate Delta Omicron variants.

Language: Английский

Citations

38
Effectiveness of SARS-CoV-2 vaccines against Omicron infection and severe events: a systematic review and meta-analysis of test-negative design studies DOI Creative Commons
Shangchen Song, Zachary J. Madewell,

Ming‐Jin Liu

et al.

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: June 9, 2023

A rapidly growing body was observed of literature evaluating the vaccine effectiveness (VE) against Omicron in test-negative design studies.

Language: Английский

Citations

29
Antigenic evolution of SARS coronavirus 2 DOI Creative Commons
Anna Z. Mykytyn, Ron A. M. Fouchier, Bart L. Haagmans

et al.

Current Opinion in Virology, Journal Year: 2023, Volume and Issue: 62, P. 101349 - 101349

Published: Aug. 28, 2023

SARS coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, emerged in China December 2019. Vaccines developed were very effective initially, however, virus has shown remarkable evolution with multiple variants spreading globally over last three years. Nowadays, newly emerging Omicron lineages are gaining substitutions at a fast rate, resulting escape from neutralization by antibodies that target Spike protein. Tools to map impact on further antigenic SARS-CoV-2, such as cartography, may be helpful update SARS-CoV-2 vaccines. In this review, we focus highlighting protein individually and combination immune escape.

Language: Английский

Citations

26
Exhaled Breath Aerosol Shedding of Highly Transmissible Versus Prior Severe Acute Respiratory Syndrome Coronavirus 2 Variants DOI Creative Commons
Jianyu Lai, Kristen K. Coleman, Sheldon Tai

et al.

Clinical Infectious Diseases, Journal Year: 2022, Volume and Issue: 76(5), P. 786 - 794

Published: Oct. 26, 2022

Abstract Background Aerosol inhalation is recognized as the dominant mode of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Three highly transmissible lineages evolved during pandemic. One hypothesis to explain increased transmissibility that natural selection favors variants with higher rates viral aerosol shedding. However, extent shedding successive SARS-CoV-2 unknown. We aimed measure infectivity and rate into exhaled breath (EBA) by individuals Delta Omicron waves compared those prior from our previously published work. Methods Individuals disease 2019 (COVID-19) (n = 93; 32 vaccinated 20 boosted) were recruited give samples, including 30-minute samples a Gesundheit-II EBA sampler. Samples quantified for RNA using reverse-transcription polymerase chain reaction cultured virus. Results Alpha 4), 3), 29) cases shed significantly more copies EBAs than infected ancestral strains not associated 57). All fully most boosted. virus 1 boosted 3 cases. Conclusions Alpha, Delta, independently high phenotypes, demonstrating convergent evolution. Vaccinated can infectious via EBA. These findings support role aerosols in transmission SARS-CoV-2. Monitoring new emerging pathogens be an important component future threat assessments guide interventions prevent

Language: Английский

Citations

36
Intrinsic and Effective Severity of Coronavirus Disease 2019 Cases Infected With the Ancestral Strain and Omicron BA.2 Variant in Hong Kong DOI
Jessica Y. Wong,

Justin Cheung,

Yun Lin

et al.

The Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 228(9), P. 1231 - 1239

Published: June 24, 2023

Understanding severity of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is crucial to inform public health measures. Here we used disease 2019 (COVID-19) patient data from Hong Kong characterize the profile COVID-19.Time-varying age-specific effective measured by case hospitalization risk fatality was estimated all individual COVID-19 collected in 23 January 2020 through 26 October 2022 over 6 epidemic waves. The intrinsic Omicron BA.2 compared estimate for ancestral strain unvaccinated patients without previous infections.With 32 222 hospitalizations 9669 deaths confirmed waves, time-varying dramatically increased <10% before largest fifth wave 41% during peak when hospital resources were severely constrained. hospitalized cases comparable estimates strain. During epidemics predominated BA.2, highest among older patients.Omicron has Wuhan strain, although substantially lower due vaccination.

Language: Английский

Citations

22
Viral kinetics of SARS-CoV-2 following onset of COVID-19 in symptomatic patients infected with the ancestral strain and omicron BA.2 in Hong Kong: a retrospective observational study DOI
Yun Lin, Peng Wu, Tim K. Tsang

et al.

The Lancet Microbe, Journal Year: 2023, Volume and Issue: 4(9), P. e722 - e731

Published: Aug. 30, 2023

Language: Английский

Citations

21
Nanomolar anti-SARS-CoV-2 Omicron activity of the host-directed TMPRSS2 inhibitor N-0385 and synergistic action with direct-acting antivirals DOI Creative Commons
Jimena Pérez‐Vargas, Gabriel Lemieux,

Connor A.H. Thompson

et al.

Antiviral Research, Journal Year: 2024, Volume and Issue: 225, P. 105869 - 105869

Published: March 26, 2024

SARS-CoV-2 Omicron subvariants with increased transmissibility and immune evasion are spreading globally alarming persistence. Whether the mutations evolution of spike (S) alter viral hijacking human TMPRSS2 for entry remains to be elucidated. This is particularly important investigate because large number diversity S reported since emergence BA.1. Here we report that a molecular determinant all clinical isolates tested in lung cells, including ancestral (BA.1, BA.2, BA.5), contemporary (BQ.1.1, XBB.1.5, EG.5.1) currently circulating BA.2.86. First, used co-transfection assay demonstrate endoproteolytic cleavage by subvariants. Second, found N-0385, highly potent inhibitor, robust inhibitor virus-like particles harbouring protein Third, show N-0385 exhibits nanomolar broad-spectrum antiviral activity against live Calu-3 cells primary patient-derived bronchial epithelial cells. Interestingly, 10-20 times more than repositioned camostat, BA.5, EG.5.1, We further shows broad synergistic clinically approved direct-acting antivirals (DAAs), i.e., remdesivir nirmatrelvir, subvariants, demonstrating potential therapeutic benefits multi-targeted treatment based on DAAs.

Language: Английский

Citations

6
Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron BA.2: a population-based study in Hong Kong DOI Creative Commons
Runhong Zhou, Na Liu, Xin Li

et al.

The Lancet Regional Health - Western Pacific, Journal Year: 2022, Volume and Issue: 32, P. 100660 - 100660

Published: Dec. 23, 2022

Language: Английский

Citations

24
SARS-CoV-2 Omicron variant shedding during respiratory activities DOI Creative Commons
Kai Sen Tan, Sean Wei Xiang Ong,

Ming Hui Koh

et al.

International Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 131, P. 19 - 25

Published: March 21, 2023

As the world transitions to COVID-19 endemicity, studies focusing on aerosol shedding of highly transmissible SARS-CoV-2 variants concern (VOCs) are vital for calibration infection control measures against VOCs that likely circulate seasonally. This follow-up Gesundheit-II sampling study aims compare patterns Omicron VOC samples with pre-Omicron analyzed in our previous study.Coarse and fine from 47 patients infected were collected during various respiratory activities (passive breathing, talking, singing) using reverse transcription-quantitative polymerase chain reaction virus culture.Compared variants, comparable RNA copy numbers detectable despite being fully vaccinated. Patients also showed a slight increase viral breathing more have persistent beyond 7 days after disease onset.This reaffirms properties should guide continued layering public health interventions even vaccinated populations.

Language: Английский

Citations

14