Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

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

Published: May 16, 2023

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that emerged through recombination of two cocirculating BA.2 lineages, BJ.1 BM.1.1.1 (a progeny BA.2.75), during summer 2022. XBB.1 variant most profoundly resistant to BA.2/5 breakthrough infection sera date more fusogenic than BA.2.75. The breakpoint located in receptor-binding domain spike, each region recombinant spike confers immune evasion increases fusogenicity. We further provide structural basis for interaction between human ACE2. Finally, intrinsic pathogenicity male hamsters comparable or even lower multiscale investigation provides evidence suggesting first observed increase its fitness rather substitutions.

Language: Английский

---

Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

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

---

The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants

MedComm, Journal Year: 2023, Volume and Issue: 4(2)

Published: March 15, 2023

As the fifth variant of concern SARS-CoV-2 virus, Omicron (B.1.1.529) has quickly become dominant type among previous circulating variants worldwide. During wave, several subvariants have emerged, with some exhibiting greater infectivity and immune evasion, accounting for their fast spread across many countries. Recently, two subvariants, BQ.1 XBB lineages, including BQ.1.1, XBB.1, XBB.1.5, a global public health issue given ability to escape from therapeutic monoclonal antibodies herd immunity induced by prior coronavirus disease 2019 (COVID-19) vaccines, boosters, infection. In this respect, which been established harbor rare mutation F486P, demonstrates superior transmissibility compared other emerged as strain in This review provides comprehensive overview epidemiological features, spike mutations, evasion lineages. We expounded on mechanisms underlying mutations neutralizing vaccinated or convalescent COVID-19 individuals (mAbs) proposed strategies prevention against sublineages.

Language: Английский

---

SARS-CoV-2 evolution in the Omicron era

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(11), P. 1952 - 1959

Published: Oct. 16, 2023

Language: Английский

---

Immune evasion and ACE2 binding affinity contribute to SARS-CoV-2 evolution

Nature Ecology & Evolution, Journal Year: 2023, Volume and Issue: 7(9), P. 1457 - 1466

Published: July 13, 2023

Language: Английский

---

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

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

---

Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 22, 2024

Background The coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although current rate Severe acute respiratory syndrome 2 (SARS-CoV-2) infections decreased significantly, long-term outlook COVID-19 remains serious cause morbidity and mortality worldwide, with still substantially surpassing even that recorded for influenza viruses. continued emergence SARS-CoV-2 variants concern (VOCs), including multiple heavily mutated Omicron sub-variants, prolonged underscores urgent need next-generation vaccine will protect from VOCs. Methods We designed multi-epitope-based incorporated B, CD4 + , CD8 T- cell epitopes conserved among all known VOCs selectively recognized by T-cells asymptomatic patients irrespective VOC infection. safety, immunogenicity, cross-protective immunity this pan-variant were studied against six using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model. Results (i) is safe (ii) induces high frequencies lung-resident functional T EM RM cells (iii) provides robust protection virus replication. COVID-19-related lung pathology death caused VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2), (B.1.1.529). Conclusion A multi-epitope bearing human B- structural non-structural antigens induced facilitated clearance, reduced morbidity, pathology,

Language: Английский

---

SARS-CoV-2 evolution on a dynamic immune landscape

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

Published: Jan. 29, 2025

Abstract Since the onset of pandemic, many SARS-CoV-2 variants have emerged, exhibiting substantial evolution in virus’ spike protein 1 , main target neutralizing antibodies 2 . A plausible hypothesis proposes that virus evolves to evade antibody-mediated neutralization (vaccine- or infection-induced) maximize its ability infect an immunologically experienced population 1,3 Because viral infection induces antibodies, may thus navigate on a dynamic immune landscape is shaped by local history. Here we developed comprehensive mechanistic model, incorporating deep mutational scanning data 4,5 antibody pharmacokinetics and regional genomic surveillance data, predict variant-specific relative number susceptible individuals over time. We show this quantity precisely matched historical variant dynamics, predicted future dynamics explained global differences dynamics. Our work strongly suggests ongoing pandemic continues shape immunity, which determines variant’s transmit, defining fitness. The model can be applied any region utilizing allows contextualizing risk assessment provides information for vaccine design.

Language: Английский

---

Implications of diversity in sperm size and function for sperm competition and fertility

The International Journal of Developmental Biology, Journal Year: 2008, Volume and Issue: 52(5-6), P. 439 - 447

Published: Jan. 1, 2008

Sperm competition is now recognised as a potent selective force shaping many male reproductive traits. While the influence of sperm on number widely accepted, its effects upon size remain controversial. It had been traditionally assumed that there trade-off between and size, so an increase in would result decrease under conditions competition. Contrary to this prediction, we proposed some time ago favours because longer swim faster are more likely win race fertilize ova. Comparative studies species show taxa such relationship exists, but consequences may vary depending environment which spermatozoa have compete. We present new evidence showing mammals at higher speeds. also mean swimming speed highly correlated with maximum speed, even if fastest fertilize, both measures informative. When individuals same compared, ratios dimensions different components, well shape head, seem better explaining velocity. Finally, determine fertility. Other shown competitive contexts, males fertilization success. conclude available supports our original hypothesis.

Language: Английский

---

Molnupiravir, Nirmatrelvir/Ritonavir, or Sotrovimab for High-Risk COVID-19 Patients Infected by the Omicron Variant: Hospitalization, Mortality, and Time until Negative Swab Test in Real Life

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(5), P. 721 - 721

Published: May 9, 2023

Background. Several drugs which are easy to administer in outpatient settings have been authorized and endorsed for high-risk COVID-19 patients with mild-moderate disease prevent hospital admission death, complementing vaccines. However, the evidence on efficacy of antivirals during Omicron wave is scanty or conflicting. Methods. This retrospective controlled study investigated Molnupiravir Nirmatrelvir/Ritonavir (Paxlovid®) Sotrovimab against standard care (controls) three different endpoints among 386 outpatients: at 30 days; death time between diagnosis first negative swab test result. Multivariable logistic regression was employed investigate determinants hospitalization due COVID-19-associated pneumonia, whereas result by means multinomial analysis as well Cox analysis. Results. Only 11 (overall rate 2.8%) developed severe pneumonia requiring hospital: 8 controls (7.2%); 2 (2.0%); 1 (1.8%). No patient institutionalized. Compared controls, less likely (aOR = 0.16; 95% CI: 0.03; 0.89) (omitted estimate); drug 84% 100% Molnupiravir. two died (rate 0.5%), both were one (a woman aged 96 years) unvaccinated other 72 had adequate vaccination status. At analysis, negativization significantly higher treated antivirals-Nirmatrelvir/Ritonavir (aHR 1.68; 1.25; 2.26) 1.45; 1.08; 1.94). 2.03; 1.51; 2.73) four 2.48; 1.32; 4.68) doses a slightly stronger effect size viral clearance. In contrast, reduced who immune-depressed 0.70; 0.52; 0.93) those Charlson index ≥5 0.63; 0.41; 0.95) started respective treatment course 3+ days after 0.56; 0.38; 0.82). Likewise, internal (excluding care), 1.74; 1.21; 2.50) 1.96; 2.93) more turn earlier than (reference category). Nonetheless, 1.91; 1.33; 2.74) 2.20; 1.06; 4.59) vaccine again associated faster rate. Again, lower if 0.54; 0.32; 0.92). Conclusions. Molnupiravir, Nirmatrelvir/Ritonavir, all effective preventing and/or mortality attributable COVID-19. hospitalizations also decreased number Although they mortality, prescription should be carefully scrutinized double opinion, not only contain health costs but reduce risk generating resistant SARS-CoV-2 strains. 64.7% fact immunized vaccines present study. High-risk prioritize vaccination, cost-effective approach pneumonia. although antivirals, especially shedding (VST) patients, an independent VST considered secondary benefit. Indeed, recommending order control rather questionable since cheap, large spectrum harmless nasal disinfectants such hypertonic saline solutions available market proven containing VST.

Language: Английский

---