Structure, Journal Year: 2024, Volume and Issue: 32(8), P. 1055 - 1067.e6
Published: July 15, 2024
Language: Английский
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
129
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: May 11, 2023
In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including R346, K444, L452, N460, F486. Here, we characterize convergent evolution of properties one recent lineage concern, BQ.1.1. Our phylogenetic analysis suggests that these five are recurrently acquired, particularly younger lineages. Epidemic dynamics modelling increase viral fitness, a large proportion fitness variation within lineages can be explained by substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 BA.5 infection sera more efficiently, as demonstrated neutralization assays. The pathogenicity hamsters is lower than BA.5. multiscale investigations illuminate evolutionary rules governing for known 2022.
Language: Английский
Citations
121
Cell Reports, Journal Year: 2022, Volume and Issue: 41(12), P. 111845 - 111845
Published: Dec. 1, 2022
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad candidate selection methods needed. Here, we describe a rational approach for identifying RBD-targeting SARS-CoV-2 cocktails. Based on high-throughput epitope determination, propose drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues focus sarbecovirus conserved sites and associate with critical viral functions, making antibody-escaping mutations less likely appear. Following these criteria, featured non-competing antibody cocktail, SA55+SA58, is identified from large collection of NAbs isolated SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating variants, could serve as prophylactics offer long-term protection, especially individuals who immunocompromised or high-risk comorbidities.
Language: Английский
Citations
101
The Lancet Infectious Diseases, Journal Year: 2022, Volume and Issue: 22(11), P. 1538 - 1540
Published: Oct. 14, 2022
Language: Английский
Citations
96
Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(11), P. 1518 - 1526.e4
Published: Sept. 28, 2022
Language: Английский
Citations
91
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
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: Jan. 3, 2023
Abstract SARS-CoV-2 recombinant subvariant XBB.1.5 is growing rapidly in the United States, carrying an additional Ser486Pro substitution compared to XBB.1 and outcompeting BQ.1.1 other XBB sublineages. The underlying mechanism for such high transmissibility remains unclear. Here we show that exhibits a substantially higher hACE2-binding affinity XBB/XBB.1. Convalescent plasma samples from BA.1, BA.5, BF.7 breakthrough infection are significantly evaded by both XBB.1.5, with displaying slightly weaker immune evasion capability than XBB.1. Evusheld Bebtelovimab could not neutralize XBB.1/XBB.1.5, while Sotrovimab weakly reactive notably, SA55 still highly effective. fact showed comparable antibody but distinct suggests enhanced receptor-binding would indeed lead growth advantages. strong hACE2 binding of also enable its tolerance further escape mutations, which should be closely monitored.
Language: Английский
Citations
74
PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(12), P. e1011868 - e1011868
Published: Dec. 20, 2023
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of the receptor-binding domain (RBD) L455F F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, HK.3. Here, we show that neutralizing antibody (NAb) evasion drives convergent F456L, while epistatic shift caused by enables subsequent convergence through ACE2 binding enhancement further immune evasion. evade RBD-targeting Class 1 public NAbs, reducing neutralization efficacy breakthrough infection (BTI) reinfection convalescent plasma. Importantly, single substitution significantly dampens receptor binding; however, combination forms an adjacent residue flipping, which leads to enhanced NAbs resistance affinity. The perturbed mode exceptional NAb evasion, revealed structural analyses. Our results indicate flexibility contributed epistasis cannot be underestimated, potential SARS-CoV-2 RBD remains high.
Language: Английский
Citations
72
Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(4), P. 100991 - 100991
Published: March 21, 2023
Emerging Omicron sub-variants are causing global concerns, and their immune evasion should be monitored continuously. We previously evaluated the escape of BA.1, BA.1.1, BA.2, BA.3 from an atlas 50 monoclonal antibodies (mAbs), covering seven epitope classes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD). Here, we update totally 77 mAbs against emerging including BQ.1.1 XBB find that BA.4/5, BQ.1.1, display further evasion. Besides, investigation into correlation binding neutralization reveals important role antigenic conformation in mAb functioning. Moreover, complex structures BA.2 RBD/BD-604/S304 BA.4/5 RBD/BD-604/S304/S309 elucidate molecular mechanism antibody by these sub-variants. By focusing on identified broadly potent mAbs, a general hotspot RBD, which could guide design vaccines calls for new broad-spectrum countermeasures COVID-19.
Language: Английский
Citations
67
Med, Journal Year: 2023, Volume and Issue: 4(11), P. 813 - 824.e4
Published: Sept. 7, 2023
Antiviral and antibody therapies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being recommended high-risk patients, but the potential development of multidrug-resistant mutations in immunocompromised patients is unclear.To investigate treatment course cases prolonged viral shedding an patient with SARS-CoV-2 infection, we conducted longitudinal measurements laboratory tests, chest computed tomography (CT) image evaluations, titers, antigen levels nasopharyngeal swabs. Furthermore, performed whole-genome sequencing digital PCR analysis to examine mechanisms drug resistance.We present a case 65-year-old man history malignant lymphoma who was treated multiple antiviral therapies, including sotrovimab, remdesivir, paxlovid (nirmatrelvir/ritonavir), molnupiravir. Initially, decreased after treatments. However, virus rebounded, showed no virologic response. The genome revealed single Omicron subvariant (BA.1.1), which evolved within host during disease progression. viruses had acquired resistance nirmatrelvir (3 chymotrypsin-like protease [3CLpro] E166 A/V), sotrovimab (spike P337L E340K), remdesivir (RNA-dependent RNA polymerase [RdRp] V166L).Our results indicate that survival fitness persist infected subpopulation selection pressure.This study supported by JSPS KAKENHI Early-Career Scientists 18K16292 (Y.H.), Grant-in-Aid Scientific Research (B) 20H03668 23H02955 YASUDA Medical Foundation Uehara Memorial Takeda Science Kato Bioscience (Y.H.).
Language: Английский
Citations
51