SARS-CoV-2 Omicron Subvariants Do Not Differ Much in Binding Affinity to Human ACE2: A Molecular Dynamics Study DOI Creative Commons
Hoang Linh Nguyen, Thai Quoc Nguyen, Mai Suan Li

et al.

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: 128(14), P. 3340 - 3349

Published: April 2, 2024

The emergence of the variant concern Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exacerbates COVID-19 pandemic due to its high contagious ability. Studies have shown that binds human ACE2 more strongly than wild type. prevalence in new cases promotes novel lineages with improved receptor binding affinity and immune evasion. To shed light on this open problem, work, we investigated free energy domain BA.2, BA.2.3.20, BA.3, BA4/BA5, BA.2.75, BA.2.75.2, BA.4.6, XBB.1, XBB.1.5, BJ.1, BN.1, BQ.1.1, CH.1.1 using all-atom molecular dynamics simulation mechanics Poisson–Boltzmann surface area method. results show these increased compared BA.1 lineage, BA.2.75 BA.2.75.2 subvariants bind others. However, general, affinities do not differ significantly from each other. electrostatic force dominates over van der Waals interaction between cells. Based our results, argue viral evolution does further improve SARS-CoV-2 for but may increase

Language: Английский

Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant DOI Creative Commons
Panke Qu, John P. Evans, Yi-Min Zheng

et al.

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(11), P. 1518 - 1526.e4

Published: Sept. 28, 2022

Language: Английский

Citations

92
Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2 DOI Creative Commons
Panke Qu, John P. Evans, Julia N. Faraone

et al.

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

Published: Oct. 20, 2022

Abstract Continued evolution of SARS-CoV-2 has led to the emergence several new Omicron subvariants, including BQ.1, BQ. 1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine neutralization resistance these as well their ancestral BA.4/5, BA.2.75 D614G variants, against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, BA.5-wave patients. We found enhanced in all especially BQ.1 BQ.1.1 subvariants driven by a key N460K mutation, lesser extent, R346T K444T mutations, BA.2.75.2 subvariant largely its F486S mutation. The also exhibited fusogenicity S processing dictated Interestingly, saw an enhancement mutation reduction D1199N processing, resulting minimal overall change. Molecular modelling revealed mechanisms receptor-binding non-receptor binding monoclonal antibody-mediated immune evasion R346T, K444T, mutations. Altogether, findings shed light on concerning newly emerging subvariants.

Language: Английский

Citations

80
Spike deep mutational scanning helps predict success of SARS-CoV-2 clades DOI Creative Commons
Bernadeta Dadonaite,

Jack Brown,

Teagan McMahon

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8021), P. 617 - 626

Published: July 3, 2024

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion

Language: Английский

Citations

53
Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6 DOI Creative Commons
Taha Y. Taha, Irene P. Chen, Jennifer M. Hayashi

et al.

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

Citations

47
Enabling the immune escaped etesevimab fully-armed against SARS-CoV-2 Omicron subvariants including KP.2 DOI Creative Commons
Chao Su,

Juanhua He,

Yufeng Xie

et al.

hLife, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
A Critical Analysis of the Use of Cilgavimab plus Tixagevimab Monoclonal Antibody Cocktail (Evusheld™) for COVID-19 Prophylaxis and Treatment DOI Creative Commons
Daniele Focosi, Arturo Casadevall

Viruses, Journal Year: 2022, Volume and Issue: 14(9), P. 1999 - 1999

Published: Sept. 9, 2022

Evusheld® (tixagevimab + cilgavimab; AZD7442) was the first anti-Spike monoclonal antibody (mAb) cocktail designed not only for treatment but also with pre-exposure prophylaxis in mind. The immunoglobulins were engineered prolonged half-life by modifying Fc fragment, thus creating a long-acting (LAAB). We review here preclinical development, baseline and treatment-emergent resistance, clinical efficacy from registration trials, real-world post-marketing evidence. combination initially approved at time of SARS-CoV-2 Delta VOC wave based on trial conducted unvaccinated subjects when Alpha dominant. Another proved as early patients led to authorization BA.4/5 wave. Tixagevimab ineffective against any Omicron sublineage, so cilgavimab has far been ingredient which made difference. Antibody monotherapy high risk selecting immune escape variants immunocompromised viral loads, nowadays represent main therapeutic indication therapies. Among sublineages, BA.1, recovered BA.2 BA.2.12.1, lost again BA.4/BA.5 BA.2.75. Our analysis indicated that used during phase without robust data this variant suggested several regulatory decisions regarding its use lacked consistency. There is an urgent need new randomized controlled trials vaccinated, subjects, using COVID-19 convalescent plasma control arm.

Language: Английский

Citations

53
The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies DOI
Daniele Focosi, Scott A. McConnell, Arturo Casadevall

et al.

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 65, P. 100882 - 100882

Published: Oct. 3, 2022

Language: Английский

Citations

41
Infection with wild-type SARS-CoV-2 elicits broadly neutralizing and protective antibodies against omicron subvariants DOI Creative Commons
Bin Ju, Qi Zhang, Ziyi Wang

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(4), P. 690 - 699

Published: March 13, 2023

Abstract The omicron variants of SARS-CoV-2 have substantial ability to escape infection- and vaccine-elicited antibody immunity. Here, we investigated the extent such in nine convalescent patients infected with wild-type during first wave pandemic. Among total 476 monoclonal antibodies (mAbs) isolated from peripheral memory B cells, identified seven mAbs broad neutralizing activity all tested, including various subvariants. Biochemical structural analysis indicated majority these bound receptor-binding domain, mimicked receptor ACE2 were able accommodate or inadvertently improve recognition substitutions. Passive delivery representative protected K18-hACE2 mice infection beta SARS-CoV-2. A deeper understanding how cells that produce could be selectively boosted recalled can augment immunity against variants.

Language: Английский

Citations

34
Immune evasion of neutralizing antibodies by SARS-CoV-2 Omicron DOI Open Access
Lidong Wang, Michelle Møhlenberg, Pengfei Wang

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2023, Volume and Issue: 70, P. 13 - 25

Published: March 5, 2023

Language: Английский

Citations

32
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

27