High fusion and cytopathy of SARS-CoV-2 variant B.1.640.1 DOI
William Bolland, Vincent Michel, Delphine Planas

et al.

Journal of Virology, Journal Year: 2023, Volume and Issue: 98(1)

Published: Dec. 13, 2023

SARS-CoV-2 variants with undetermined properties have emerged intermittently throughout the COVID-19 pandemic. Some possess unique phenotypes and mutations which allow further characterization of viral evolution Spike functions. Around 1,100 cases B.1.640.1 variant were reported in Africa Europe between 2021 2022, before expansion Omicron. Here, we analyzed biological a isolate its Spike. Compared to ancestral Spike, carried 14 amino acid substitutions deletions. escaped binding by some anti-N-terminal domain anti-receptor-binding monoclonal antibodies, neutralization sera from convalescent vaccinated individuals. In cell lines, infection generated large syncytia high cytopathic effect. primary airway cells, replicated less than Omicron BA.1 triggered more death other variants. The was highly fusogenic when expressed alone. This mediated two poorly characterized infrequent located S2 domain, T859N D936H. Altogether, our results highlight cytopathy hyper-fusogenic variant, supplanted upon emergence BA.1. (This study has been registered at ClinicalTrials.gov under registration no. NCT04750720.)IMPORTANCEOur plasticity generate strains causative being uncharacterized previous We describe mechanisms regulating formation subsequent consequences culture model, are understood.

Language: Английский

Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant DOI Creative Commons
Khadija Khan, Gila Lustig,

Cornelius Römer

et al.

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

Published: Dec. 6, 2023

Abstract Omicron BA.2.86 subvariant differs from BA.2 as well recently circulating variants by over 30 mutations in the spike protein alone. Here we report on isolation of live a diagnostic swab collected South Africa which tested for escape neutralizing antibodies and viral replication properties cell culture. We found that does not have significantly more relative to XBB.1.5 immunity elicited either XBB-family infection or residual sera African population. extensive ancestral virus with D614G substitution (B.1 lineage) when neutralized pre-Omicron vaccinated individuals BA.1 infected individuals. show similar dynamics VeroE6-TMPRSS2 H1299-ACE2 lines. also investigate relationship sequences. The closest sequences are samples Southern early 2022. Similarly, many basal were sampled Africa. This suggests potentially evolved this region, unobserved evolution led scale strains SARS-CoV-2.

Language: Английский

Citations

71
Virological characteristics of the SARS-CoV-2 BA.2.86 variant DOI Creative Commons
Tomokazu Tamura,

Keita Mizuma,

Hesham Nasser

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(2), P. 170 - 180.e12

Published: Jan. 26, 2024

In late 2023, several SARS-CoV-2 XBB descendants, notably EG.5.1, were predominant worldwide. However, a distinct lineage, the BA.2.86 variant, also emerged. is phylogenetically from other Omicron sublineages, accumulating over 30 amino acid mutations in its spike protein. Here, we examined virological characteristics of variant. Our epidemic dynamics modeling suggested that relative reproduction number significantly higher than EG.5.1. Additionally, four clinically available antivirals effective against BA.2.86. Although fusogenicity similar to parental BA.2 spike, intrinsic pathogenicity hamsters was lower BA.2. Since growth kinetics are those both vitro and vivo, attenuated likely due decreased replication capacity. These findings uncover features BA.2.86, providing insights for control treatment.

Language: Английский

Citations

61
Humoral immune escape by current SARS-CoV-2 variants BA.2.86 and JN.1, December 2023 DOI Creative Commons
Lara M. Jeworowski, Barbara Mühlemann, Felix Walper

et al.

Eurosurveillance, Journal Year: 2024, Volume and Issue: 29(2)

Published: Jan. 11, 2024

Variant BA.2.86 and its descendant, JN.1, of SARS-CoV-2 are rising in incidence across Europe globally. We isolated recent BA.2.86, EG.5, XBB.1.5 earlier variants. tested live virus neutralisation sera taken September 2023 from vaccinated exposed healthy persons (n = 39). found clear escape against variants but no specific pronounced for or JN.1. Neutralisation corresponds to variant predominance may not be causative the upsurge JN.1 incidence.

Language: Английский

Citations

56
Safety and Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine in Individuals ≥12 Years Old: A Phase 2/3 Trial DOI Creative Commons

Juleen Gayed,

Oyeniyi Diya,

Francine S. Lowry

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 118 - 118

Published: Jan. 24, 2024

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of ongoing, open-label, phase 2/3 study monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy participants ≥12 years old (N = 412 (12–17 years, N 30; 18–55 174; >55 208)) who previously received ≥3 doses US-authorized mRNA vaccine, the most recent being BA.4/BA.5-adapted bivalent vaccine ≥150 days before vaccination, were vaccinated. Serum 50% neutralizing titers XBB.1.5, EG.5.1, BA.2.86 measured 7 1 month after vaccination in subset ≥18-year-olds 40) positive for SARS-CoV-2 at baseline. Seven-day was also evaluated matched group previous (ClinicalTrials.gov Identifier: NCT05472038). There no new signals; local reactions systemic events mostly mild to moderate severity, adverse infrequent, none led withdrawal. The induced numerically higher than robust responses all three sublineages month. These support favorable benefit-risk profile 30 μg. ClinicalTrials.gov NCT05997290

Language: Английский

Citations

24
Evolution of the SARS-CoV-2 Omicron Variants: Genetic Impact on Viral Fitness DOI Creative Commons
Wenhao Liu, Zehong Huang, Jin Xiao

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 184 - 184

Published: Jan. 25, 2024

Over the last three years, pandemic of COVID-19 has had a significant impact on people’s lives and global economy. The incessant emergence variant strains compounded challenges associated with management COVID-19. As predominant from late 2021 to present, Omicron its sublineages, through continuous evolution, have demonstrated iterative viral fitness. comprehensive elucidation biological implications that catalyzed this evolution remains incomplete. In accordance extant research evidence, we provide review subvariants Omicron, delineating alterations in immune evasion, cellular infectivity, cross-species transmission potential. This seeks clarify underpinnings biology within SARS-CoV-2, thereby providing foundation for strategic considerations post-pandemic era

Language: Английский

Citations

23
Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion DOI Creative Commons

Song Xue,

Yuru Han, Fan Wu

et al.

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(6), P. 403 - 418

Published: March 4, 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within receptor binding domain (RBD) spike (S) protein, lead to functional alteration both engagement monoclonal antibody (mAb) recognition. Here, we review data RBD point mutations possessed by major discuss their individual effects on ACE2 affinity immune evasion. Many single amino acid substitutions epitopes crucial for evasion capacity may conversely weaken affinity. However, this weakened effect could be largely compensated specific epistatic such as N501Y, thus maintaining overall protein all variants. The predominant direction evolution lies neither promoting nor evading mAb neutralization but a delicate balance between these two dimensions. Together, interprets how efficiently resist meanwhile is maintained, emphasizing significance comprehensive assessment mutations.

Language: Английский

Citations

21
Anticipating the future of the COVID-19 pandemic: insights into the emergence of SARS-CoV-2 variant JN.1 and its projected impact on older adults DOI Open Access
Jorge Quarleri, M. Victoria Delpino, Verónica Galván

et al.

GeroScience, Journal Year: 2024, Volume and Issue: 46(3), P. 2879 - 2883

Published: Jan. 10, 2024

Language: Английский

Citations

19
Sotrovimab: A Review of Its Efficacy against SARS-CoV-2 Variants DOI Creative Commons
Daniele Focosi, Arturo Casadevall, Massimo Franchini

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 217 - 217

Published: Jan. 31, 2024

Among the anti-Spike monoclonal antibodies (mAbs), S-309 derivative sotrovimab was most successful in having longest temporal window of clinical use, showing a high degree resiliency to SARS-CoV-2 evolution interrupted only by appearance BA.2.86* variant interest (VOI). This success undoubtedly reflects rational selection target highly conserved epitope coronavirus Spike proteins. We review here efficacy against different variants outpatients and inpatients, discussing both randomized controlled trials real-world evidence. Although it could not be anticipated at time its development introduction, sotrovimab's use immunocompromised individuals who harbor large populations viruses created conditions for eventual demise, as antibody viral led withdrawal due inefficacy later lineages. Despite this, based on observational data, some authorities have continued promote sotrovimab, but lack binding newer strongly argues futility use. The story highlights power modern biomedical science generate novel therapeutics while also providing cautionary tale need devise strategies minimize emergence resistance antibody-based therapeutics.

Language: Английский

Citations

19
Evolution of the SARS-CoV-2 Omicron spike DOI Creative Commons
Ruth Parsons, Priyamvada Acharya

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113444 - 113444

Published: Nov. 18, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern, first identified in November 2021, rapidly spread worldwide and diversified into several subvariants. spike (S) protein accumulated an unprecedented number sequence changes relative to previous variants. In this review, we discuss how S structural features modulate host cell receptor binding, virus entry, immune evasion highlight these differentiate from We also examine key properties track across the still-evolving subvariants importance continuing surveillance evolution over time.

Language: Английский

Citations

35
Virus isolation and neutralisation of SARS-CoV-2 variants BA.2.86 and EG.5.1 DOI Open Access
Ria Lassaunière, Charlotta Polacek,

Magdalena Utko

et al.

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(12), P. e509 - e510

Published: Nov. 7, 2023

Language: Английский

Citations

32