SARS-CoV-2 Spike N-Terminal Domain Engages 9-O-Acetylated α2–8-Linked Sialic Acids DOI Creative Commons
Ilhan Tomris, Luca Unione, Linh Nguyen

и другие.

ACS Chemical Biology, Год журнала: 2023, Номер 18(5), С. 1180 - 1191

Опубликована: Апрель 27, 2023

SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the protein contains C-terminal binding (RBD) and an N-terminal (NTD). NTD other coronaviruses includes glycan cleft. However, for NTD, protein–glycan was only observed weakly sialic acids highly sensitive methods. Amino acid changes in variants concern (VoC) show antigenic pressure, which can be indication NTD-mediated binding. Trimeric proteins SARS-CoV-2, alpha, beta, delta, omicron did not reveal capability. Unexpectedly, beta subvariant strain (501Y.V2-1) to Vero E6 cells sialidase pretreatment. Glycan microarray analyses identified putative 9-O-acetylated ligand, confirmed by catch-and-release ESI-MS, STD-NMR analyses, graphene-based electrochemical sensor. variant attained enhanced modality specificity toward structures, suggesting dual-receptor functionality domain, quickly selected against. These results indicate that probe additional evolutionary space, allowing receptors on surface target cells.

Язык: Английский

Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants DOI Creative Commons
Qian Wang, Sho Iketani, Zhiteng Li

и другие.

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

Процитировано

788
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution DOI Creative Commons
Yunlong Cao, Fanchong Jian, Jing Wang

и другие.

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

Процитировано

582
Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses DOI Open Access
Yanjia Chen, Xiaoyu Zhao, Hao Zhou

и другие.

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

Опубликована: Сен. 27, 2022

Язык: Английский

Процитировано

286
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution DOI Creative Commons
Yunlong Cao, Fanchong Jian, Jing Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Сен. 16, 2022

Abstract Continuous evolution of Omicron has led to a rapid and simultaneous emergence numerous variants that display growth advantages over BA. 5. Despite their divergent evolutionary courses, mutations on receptor-binding domain (RBD) converge several hotspots. The driving force destination such convergent its impact humoral immunity remain unclear. Here, we demonstrate these can cause striking evasion neutralizing antibody (NAb) drugs convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability. BQ.1.1.10, BA.4.6.3, XBB, CH. 1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level. To delineate origin evolution, determined escape mutation profiles neutralization activity monoclonal antibodies (mAbs) isolated BA.2 breakthrough-infection convalescents. Importantly, due immune imprinting, especially infection caused significant reductions in epitope diversity NAbs increased proportion non-neutralizing mAbs, which turn concentrated pressure promoted evolution. Moreover, showed RBD could be accurately inferred by integrated deep mutational scanning (DMS) profiles, trends BA.2.75/BA.5 subvariants well-simulated through constructed pseudovirus mutants. Together, our results suggest current herd vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines NAb development should highly prioritized, mutants help examine effectiveness advance.

Язык: Английский

Процитировано

218
Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike DOI
Qian Wang, Yicheng Guo, Liyuan Liu

и другие.

Nature, Год журнала: 2023, Номер 624(7992), С. 639 - 644

Опубликована: Окт. 23, 2023

Язык: Английский

Процитировано

160
Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75 DOI Creative Commons
Yunlong Cao,

Weiliang Song,

Lei Wang

и другие.

Cell Host & Microbe, Год журнала: 2022, Номер 30(11), С. 1527 - 1539.e5

Опубликована: Окт. 4, 2022

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity host receptor angiotensin-converting enzyme 2 (ACE2) than other variants. Structural analyses of spike shows its decreased thermostability increased frequency binding domain (RBD) "up" conformation under acidic conditions, suggesting low-pH-endosomal cell entry. Relative to BA.4/BA.5, reduced evasion humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater Delta plasma. also weaker neutralization against mainly due BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld Bebtelovimab effective BA.2.75. These results suggest may prevail after receptor-binding capability could support further immune-evasive mutations.

Язык: Английский

Процитировано

159
Antibody-mediated neutralization of SARS-CoV-2 DOI Creative Commons

Henning Gruell,

Kanika Vanshylla, Timm Weber

и другие.

Immunity, Год журнала: 2022, Номер 55(6), С. 925 - 944

Опубликована: Май 13, 2022

Язык: Английский

Процитировано

123
Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75 DOI Creative Commons
Qian Wang, Sho Iketani, Zhiteng Li

и другие.

Cell Host & Microbe, Год журнала: 2022, Номер 30(11), С. 1512 - 1517.e4

Опубликована: Сен. 6, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently circulating BA.2, raising concerns that it may further evade vaccine-elicited therapeutic antibodies. We found moderately more neutralization resistant sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar BA.2.12.1 (1.1-fold), but sensitive BA.4/5 (0.6-fold). Relative showed heightened resistance class 1 3 monoclonal antibodies targeting spike-receptor-binding domain while gaining sensitivity Resistance was largely conferred by G446S R460K mutations. slightly (3.7-fold) bebtelovimab, a antibody potent activity against all subvariants. also exhibited higher binding affinity host receptor ACE2 other provides insight into SARS-CoV-2 evolution as gains transmissibility incrementally evading neutralization.

Язык: Английский

Процитировано

99
Impact of antigenic evolution and original antigenic sin on SARS-CoV-2 immunity DOI Creative Commons

Muriel Aguilar-Bretones,

Ron A. M. Fouchier, Marion Koopmans

и другие.

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(1)

Опубликована: Янв. 2, 2023

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccinations targeting the spike protein (S) offer protective immunity against disease 2019 (COVID-19). This may further be shaped by cross-reactivity common cold coronaviruses. Mutations arising in S that are associated altered intrinsic virus properties immune escape result continued circulation of SARS-CoV-2 variants. Potentially, vaccine updates will required to protect future variants concern, as for influenza. To potent protection variants, these second-generation vaccines need redirect epitopes not merely boost toward conserved domains preimmune individuals. For influenza, efficacy repeated vaccination is hampered original antigenic sin, an attribute memory leads greater induction antibodies specific first-encountered variant immunogen compared subsequent In this Review, recent findings on sin discussed context evolution. Unanswered questions directions highlighted, emphasis impact outcome design.

Язык: Английский

Процитировано

88
SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines DOI Creative Commons
John E. Bowen, Young‐Jun Park, Cameron Stewart

и другие.

Science Immunology, Год журнала: 2022, Номер 7(78)

Опубликована: Ноя. 10, 2022

Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies engineering strategies. We show here containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of the

Язык: Английский

Процитировано

74