SARS-CoV-2 variant biology: immune escape, transmission and fitness

Nature Reviews Microbiology, Год журнала: 2023, Номер unknown

Опубликована: Янв. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Язык: Английский

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Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Cell, Год журнала: 2022, Номер 186(2), С. 279 - 286.e8

Опубликована: Дек. 14, 2022

The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization BQ.1, BQ.1.1, XBB, XBB.1 by sera vaccinees infected persons was markedly impaired, including individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against were lower 13- 81-fold 66- 155-fold, respectively, far beyond what had been observed date. Monoclonal antibodies capable neutralizing the original variant largely inactive these new subvariants, responsible individual mutations identified. These found have similar ACE2-binding affinities as predecessors. Together, our findings indicate present serious threats current COVID-19 vaccines, render all authorized antibodies, may gained dominance in population because advantage evading antibodies.

Язык: Английский

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Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Nature, Год журнала: 2022, Номер unknown

Опубликована: Дек. 19, 2022

Abstract Continuous evolution of Omicron has led to a rapid and simultaneous emergence numerous variants that display growth advantages over BA.5 (ref. 1 ). Despite their divergent evolutionary courses, mutations on receptor-binding domain (RBD) converge several hotspots. The driving force destination such sudden convergent its effect humoral immunity remain unclear. Here we demonstrate these can cause evasion neutralizing antibody drugs convalescent plasma, including those from breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB CH.1.1 are the most antibody-evasive strains tested. To delineate origin evolution, determined escape mutation profiles neutralization activity monoclonal antibodies isolated individuals who had BA.2 infections 2,3 . Owing immune imprinting, especially infection reduced diversity binding sites increased proportions non-neutralizing clones, which, in turn, focused pressure promoted RBD. Moreover, show RBD could be accurately inferred by deep mutational scanning 4,5 , trends BA.2.75 subvariants well foreseen through constructed pseudovirus mutants. These results suggest current herd vaccine boosters may not efficiently prevent variants.

Язык: Английский

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Therapeutic strategies for COVID-19: progress and lessons learned

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(6), С. 449 - 475

Опубликована: Апрель 19, 2023

Язык: Английский

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Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir

Nature, Год журнала: 2022, Номер 613(7944), С. 558 - 564

Опубликована: Ноя. 9, 2022

Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19 (refs. 1,2). However, because SARS-CoV-2 evolved become resistant other therapeutic modalities3-9, there is a concern that same could occur for nirmatrelvir. Here we examined this possibility by in vitro passaging nirmatrelvir using two independent approaches, including one on large scale. Indeed, highly viruses emerged from both and their sequences showed multitude mutations. In experiment peformed with many replicates, 53 viral lineages were selected mutations observed at 23 different residues enzyme. Nevertheless, several common mutational pathways resistance preferred, majority descending T21I, P252L or T304I as precursor Construction analysis 13 recombinant clones these mediated only low-level resistance, whereas greater required accumulation additional E166V mutation conferred strongest (around 100-fold), but resulted loss replicative fitness was restored compensatory changes such L50F T21I. Our findings indicate does readily arise via multiple vitro, specific herein form strong foundation which study mechanism detail inform design next-generation inhibitors.

Язык: Английский

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Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses

Nature reviews. Immunology, Год журнала: 2022, Номер 23(3), С. 189 - 199

Опубликована: Сен. 27, 2022

Язык: Английский

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

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Май 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.

Язык: Английский

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Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB

New England Journal of Medicine, Год журнала: 2022, Номер 388(1), С. 89 - 91

Опубликована: Дек. 7, 2022

Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB To the Editor: Three sublineages B.1.1.529(omicron) variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have serially transitioned into globally dominant formsfirst BA.1, then BA.2, BA.5.As October 2022, most circulating omicron variants belong to BA.5.However, prevalence (a BA.5 subvariant) BA.2 is increasing rapidly in several countries, including United States India.BA.2 been shown less sensitivity certain monoclonal antibodies than previously concern. 1-5Notably, as compared with carry additional substitutions receptor-binding domain spike (S) protein, which major target for vaccines therapeutic disease 2019 (Covid-19).These subvariants may, therefore, be more immune-evasive BA.2.We assessed efficacy (hCoV-19/ Japan/TY41-796/2022; TY41-796) (hCoV-19/Japan/TY41-795/2022; TY41-795), were isolated from patients.The isolate had three (R346T, K444T, N460K) its a (hCoV-19/Japan/TY41-702/2022) (Fig. S1A Supplementary Appendix, available full text this letter at NEJM.org).The nine changes (G339H, R346T, L368I, V445P, G446S, N460K, F486S, F490S, wild-type amino acid position 493) (hCoV-19/Japan/UT-NCD1288-2N/2022)

Язык: Английский

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Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5

Cell, Год журнала: 2022, Номер 185(21), С. 3992 - 4007.e16

Опубликована: Сен. 14, 2022

After the global spread of SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that effective reproduction numbers these subvariants are greater than original BA.2. Neutralization experiments revealed immunity induced by BA.1/2 infections is less against BA.4/5. Cell culture BA.2.12.1 BA.4/5 replicate more efficiently human alveolar epithelial cells particularly, fusogenic We further provided structure spike receptor-binding domain binds to ACE2 considered how substitutions play roles binding immune evasion. Moreover, using hamsters suggested pathogenic multiscale investigations suggest risk particularly BA.4/5, health

Язык: Английский

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Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2

Cell Host & Microbe, Год журнала: 2022, Номер 31(1), С. 9 - 17.e3

Опубликована: Ноя. 22, 2022

Язык: Английский

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