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

Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike DOI
Qian Wang, Yicheng Guo, Liyuan Liu

et al.

Nature, Journal Year: 2023, Volume and Issue: 624(7992), P. 639 - 644

Published: Oct. 23, 2023

Language: Английский

Citations

156
Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion DOI Creative Commons
Delphine Planas, Isabelle Staropoli, Vincent Michel

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 13, 2024

Abstract The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicate IGROV-1 no longer Vero E6 are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhances NAb against both BA.2.86 displays affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Language: Английский

Citations

128
Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants DOI Creative Commons
Panke Qu, Kai Xu, Julia N. Faraone

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 585 - 595.e6

Published: Jan. 8, 2024

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose-vaccinated bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, monoclonal antibody (mAb) S309. We assessed biology spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially different conformational stability spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Language: Английский

Citations

105
SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency DOI Creative Commons
Lu Zhang,

Amy Kempf,

Inga Nehlmeier

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 596 - 608.e17

Published: Jan. 8, 2024

Language: Английский

Citations

78
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

72
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

63
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
Interim Report of the Reactogenicity and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 XBB–Containing Vaccines DOI Creative Commons

Spyros Chalkias,

Nichole McGhee,

Jordan L. Whatley

et al.

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: 230(2), P. e279 - e286

Published: Feb. 13, 2024

Monovalent Omicron XBB.1.5-containing vaccines were approved for coronavirus disease 2019 (COVID-19) 2023-2024 immunizations.

Language: Английский

Citations

49
Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1 DOI Creative Commons
Yanping Hu, Jing Zou, Chaitanya Kurhade

et al.

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(2)

Published: Oct. 12, 2023

The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live neutralization assay compare the evasion ability of BA.2.86 other emerged subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 FL.1.5.1. Our results show that is less evasive than sublineages. EG.5.1, FL.1.5.1 continue significantly induced by parental mRNA vaccine BA.5 Bivalent booster. Notably, when compared more recent descendants, particularly display increased resistance neutralization. Among all tested CH.1.1 exhibits greatest evasion. contrast, XBC.1.6 shows slight reduction but remains comparably sensitive BA.5. Furthermore, XBB.1.5-breakthrough infection enhances breadth potency cross-neutralization. These findings reinforce expectation upcoming would likely boost currently circulating while also underscoring critical importance ongoing surveillance monitor evolution immune variants.

Language: Английский

Citations

46
Neutralization escape, infectivity, and membrane fusion of JN.1-derived SARS-CoV-2 SLip, FLiRT, and KP.2 variants DOI Creative Commons

Pei Li,

Julia N. Faraone, Cheng Chih Hsu

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114520 - 114520

Published: July 17, 2024

Highlights•SLip, FLiRT, and KP.2 are poorly neutralized by bivalent-vaccinated sera•XBB.1.5-vaccinated hamster JN.1 patient sera SLip, KP.2•S mutations R346T, L455S, F456L alter ACE2 binding neutralization epitopes•SLip, spikes exhibit less fusion processing relative to JN.1SummaryWe investigate JN.1-derived subvariants for antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared JN.1, KP.2, especially FLiRT increased resistance BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated robustly neutralize but have reduced efficiency SLip. All resistant S309 show decreased infectivity, cell-cell fusion, spike JN.1. Modeling reveals that L455S SLip reduce ACE2, while R346T strengthens it. These three mutations, alongside D339H, key epitopes spike, likely explaining the sensitivity of these neutralization. Our findings highlight suggest future vaccine formulations should consider as an immunogen, although current monovalent could still offer adequate protection.Graphical abstract

Language: Английский

Citations

33