Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike DOI Creative Commons
Timothy J.C. Tan, Abby Odle, Ruipeng Lei

et al.

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

Published: Sept. 28, 2023

ABSTRACT Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding spike protein. In contrast, whether antigenic occurs S2 remains largely elusive. Here, we perform a deep mutational scanning experiment to identify that affect three apex public antibodies. Our results indicate spatially diverse mutations, including D950N Q954H, which are observed Delta Omicron variants, respectively, weaken these Although antibodies known be non-neutralizing, show they confer partial protection vivo . We further demonstrate such activity diminished natural mutation D950N. Overall, this study indicates can undergo drift, represents potential challenge for development more universal coronavirus vaccines.

Language: Английский

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
Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike DOI Creative Commons
Timothy J.C. Tan, Abhishek Kumar Verma, Abby Odle

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(15)

Published: April 1, 2024

Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding spike protein. In contrast, whether antigenic occurs S2 remains largely elusive. Here, we perform a deep mutational scanning experiment to identify that affect three apex public antibodies. Our results indicate spatially diverse mutations, including D950N Q954H, which are observed Delta Omicron variants, respectively, weaken these Although antibodies known be nonneutralizing, show they confer protection vivo through Fc-mediated effector functions. Overall, this study indicates can undergo drift, represents potential challenge for development more universal coronavirus vaccines.

Language: Английский

Citations

9
SARS-CoV-2 genomic evolution during a severe and long-lasting omicron infection under antiviral therapy DOI Creative Commons

Matteo Bolis,

Sara Uceda Renteria, Laura Alagna

et al.

BMC Infectious Diseases, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 13, 2025

Prolonged SARS-CoV-2 infection observed in immunocompromised individuals even the presence of antiviral treatment provides opportunities for viruses to evolve immune escape and drug-resistant variants. A 72-year-old male with IgG4-related disease was admitted Emergency Department a city Hospital Milan then transferred Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico December 2023, due respiratory distress diagnosed November 2023. After 117 days since onset infection, two cycles sotrovimab/remdesivir combined therapy, clinical improvement allowed hospital discharge, notwithstanding persistent positivity. Fifteen later, patient re-admitted worsening conditions. third cycle therapy prolonged nirmatrelvir/ritonavir, nasopharyngeal load dropped conditions improved, ending successful discharge. whole genome sequences, obtained at six time-points showed an FL.1.5.1 recombinant form genetic distance median (IQR) 0.00052 (0.00041–0.00066) similar among 43 contemporaneous forms (p = 0.098). De novo SNPs were all time points, peak (n 70) day 133 corresponding second hospitalization. Six non-synonymous mutations (three RdRp three spike protein, four them known be associated drug resistance) appeared transiently, after fourth course sotrovimab 500 mg/remdesivir combination. Five de SNPs, fixed over long-lasting infection. The N856K, reduced fusogenicity infectivity Omicron BA.1, completely replaced by constitutive N 136. This case confirms intra-host evolution dynamics immunocompromised, prolonged-infected individual, involving positions resistance fusogenic traits SARS-CoV-2. These results underscore importance early detection individuals, its rapid containment using highly effective treatment, limit serious complications risk new potentially concerning viral variants emergence.

Language: Английский

Citations

0
Structural understanding of SARS-CoV-2 virus entry to host cells DOI Creative Commons

Kim Le,

Shrute Kannappan, Truc Kim

et al.

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Nov. 2, 2023

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants virus have further exacerbated COVID-19 mortality and infection rates, emphasizing urgent need for effective preventive strategies. Understanding viral mechanism crucial developing therapeutics vaccines. The entry SARS-CoV-2 into host cells key step in pathway has been targeted drug development. Despite numerous reviews virus, there lack comprehensive focusing on structural aspects entry. In this review, we analyze changes Spike proteins during process, dividing process prebinding, receptor binding, proteolytic cleavage, membrane fusion steps. By understanding atomic-scale details entry, can better target intervention We also examine impacts mutations proteins, including Omicron variant, Structural information provides insights effects guide development Finally, discuss available structure-based approaches Overall, review detailed analysis highlighting its significance vaccines against COVID-19. Therefore, our emphasizes importance combating infection.

Language: Английский

Citations

10
Soluble Angiotensin-Converting Enzyme 2 Protein Improves Survival and Lowers Viral Titers in Lethal Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Type 2 Infection with the Delta Variant DOI Creative Commons
Cosimo Cianfarini, Luise Hassler, Jan Wysocki

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 203 - 203

Published: Jan. 23, 2024

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) utilizes angiotensin-converting enzyme (ACE2) as its main receptor for cell entry. We bioengineered a soluble ACE2 protein termed 618-DDC-ABD that has increased binding to SARS-CoV-2 and prolonged duration of action. Here, we investigated the protective effect this when administered intranasally k18-hACE2 mice infected with aggressive Delta variant. were variant by inoculation lethal dose (2 × 104 PFU). (10 mg/kg) or PBS was six hours prior 24 48 h post-viral inoculation. All animals in control group succumbed disease on day seven post-infection (0% survival), whereas, contrast, there only one casualty received (90% survival). Mice had minimal assessed using clinical score stable weight, both brain lung viral titers markedly reduced. These findings demonstrate efficacy decoy an extended action protecting against Together previous work, these underline universal potential current future emerging variants.

Language: Английский

Citations

3
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

Citations

8
SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant DOI Creative Commons
Cédric Garcia,

Baptiste Compagnon,

Agnès Ribes

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 27, 2023

In November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating COVID-19 pandemic over world. displays a number mutations, particularly in spike protein, leading to specific characteristics including higher potential for transmission. Although caused significant deaths worldwide, it generally induces less severe clinical signs compared earlier variants. As its impact on blood platelets remains unknown, we investigated platelet behavior patients infected with comparison Delta. Clinical biological (n=9) or Delta (n=11) variants were analyzed. Using complementary methods such as flow cytometry, confocal imaging electron microscopy, examined activation, responsiveness phenotype, presence virus induction selective autophagy. We also explored direct effect proteins from healthy signaling. Severe infection resulted activation partial desensitization, autophagy response. The intraplatelet processing viral cargo was different evidenced by distribution protein-positive structures near plasma membrane colocalization Rab7. Moreover, alone activated signaling pathways phosphorylation AKT, p38MAPK, LIMK SPL76 kinetics. prior variants, leads desensitization previously observed variant. found where autophagy, but mechanisms cargo, part innate response, differs Delta, suggesting that mutations protein modify interactions.

Language: Английский

Citations

7
SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages DOI Creative Commons
Aldo Barrera, Constanza Martínez-Valdebenito, Jenniffer Angulo

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 29, 2024

Since the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, immune evasion. By first trimester 2023 Chile, as most countries, BQ XBB were predominant circulating sub-lineages Omicron. The molecular antigenic characteristics these have been mainly determined using non-authentic spike pseudoviruses, which is often described limitation. Additionally, few comparative studies isolates from recent Omicron conducted. In this study, we isolated clinical samples, including ancestral B.1.1, Delta, BA.1, BA.2 BA.5. We assessed their infectivity through cell culture infections antibody evasion neutralization assays. observed variations plaque size, morphology, cytotoxicity upon infection Vero E6-TMPRSS2 cells for each variant compared B.1.1 virus. BA.2-derived sub-variants, such XBB.1.5, showed attenuated replication, while BA.5-derived variants, BQ.1.1, exhibited replication rates similar Similar trends intestinal Caco-2 cells, except Delta. Antibody experiments sera individuals infected during COVID-19 wave (FWI) consistent but moderate reduction against sub-lineages. Interestingly, despite being less prevalent, BQ.1.1 6.1-fold greater escape than XBB.1.5. Neutralization patterns when tested vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules. However, CCP 2.3-fold higher XBB.1.5 FWI PPP sera. This study provides new insights into differences between leading eventual outcompetition. Our analysis offers important evidence regarding balance that drives evolution second-generation population.

Language: Английский

Citations

1
Dynamic expedition of leading mutations in SARS-CoV-2 spike glycoproteins DOI Creative Commons
Muhammad Abul Hasan, Zhouyi He, M Jia

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 23, P. 2407 - 2417

Published: May 24, 2024

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the recent pandemic, has generated countless new variants with varying fitness. Mutations spike glycoprotein play a particularly vital role in shaping its evolutionary trajectory, as they have capability to alter infectivity and antigenicity. We present time-resolved statistical method, Dynamic Expedition Leading (deLemus), analyze dynamics SARS-CoV-2 glycoprotein. proposed

Language: Английский

Citations

0
Prone-to-Infectivity of Omicron BA.2 Subvariant from Indonesia on ACE-2 Expressing Cell Lines DOI Creative Commons

Wahyu Hidayati,

Desti Hidayati,

Fathur Luthfiano Khairindra

et al.

Journal of Advanced Research in Micro and Nano Engieering, Journal Year: 2024, Volume and Issue: 21(1), P. 54 - 65

Published: July 31, 2024

SARS-CoV-2 virus undergoes mutation, leading to the virus's evolution and modifications in characteristics of virus. Omicron, including BA.2 subvariant, is currently predominant variant infection. There are no reports regarding its properties or utilization Indonesian isolate for therapy vaccine development. Therefore, this study evaluated appropriate host cells Omicron via susceptibility tests. The from Indonesia was exposed three mammalian-ACE2-expressing cell lines. Sharing amino acids between previous VOC subvariants performed using a simple silico comparison method. results showed that could not infect HepG2 Huh-7D12 due foci forming on those Moreover, we also found has unique acid alteration spike protein. According findings, propagate Vero E6 lines, mutations play role changing infection mechanism. A deeper vitro experiment enhance findings by comparing all sequences analyzing mechanism each single mutation pseudovirus.

Language: Английский

Citations

0