Dynamin independent endocytosis is an alternative cell entry mechanism for multiple animal viruses DOI Creative Commons
Ravi Ojha, Anmin Jiang, Elina Mäntylä

и другие.

PLoS Pathogens, Год журнала: 2024, Номер 20(11), С. e1012690 - e1012690

Опубликована: Ноя. 14, 2024

Mammalian receptor-mediated endocytosis (RME) often involves at least one of three isoforms the large GTPase dynamin (Dyn). Dyn pinches-off vesicles plasma membrane and mediates uptake many viruses, although some viruses directly penetrate membrane. RME is classically interrogated by genetic pharmacological interference, but this has been hampered undesired effects. Here we studied virus entry in conditional knock-out (KO) mouse embryonic fibroblasts lacking expression all (Dyn-KO-MEFs). The small canine parvovirus known to use a single receptor, transferrin strictly depended on dynamin. Larger or multiple receptors, including alphaviruses, influenza, vesicular stomatitis, bunya, adeno, vaccinia, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rhinoviruses infected Dyn-KO-MEFs, albeit higher dosage than wild-type MEFs. In absence transmembrane protease serine subtype (TMPRSS2), which normally activates SARS-CoV-2 spike protein for fusion, angiotensin-converting enzyme (ACE2)-expressing MEFs predominantly through dynamin- actin-dependent endocytosis. presence TMPRSS2 ancestral Wuhan-strain bypassed both dynamin-dependent -independent endocytosis, was less sensitive endosome maturation inhibitors Omicron B1 XBB variants, supporting notion that variants do not efficiently TMPRSS2. Collectively, our study suggests function endocytic pits can be essential infection with single-receptor while it increases efficiency multi-receptor otherwise rely functional actin network infection.

Язык: Английский

SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency DOI Creative Commons
Lu Zhang,

Amy Kempf,

Inga Nehlmeier

и другие.

Cell, Год журнала: 2024, Номер 187(3), С. 596 - 608.e17

Опубликована: Янв. 8, 2024

Язык: Английский

Процитировано

78
COVID-19 drug discovery and treatment options DOI
Jasper Fuk‐Woo Chan, Shuofeng Yuan, Hin Chu

и другие.

Nature Reviews Microbiology, Год журнала: 2024, Номер 22(7), С. 391 - 407

Опубликована: Апрель 15, 2024

Язык: Английский

Процитировано

20
Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue DOI Creative Commons

Guoli Shi,

Tiansheng Li, Kin Kui Lai

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 30, 2024

Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue spread. Here, we show exhibits increased infectivity in primary adult upper airway tissue relative Delta. Using recombinant forms nasal epithelial cells cultured at the liquid-air interface, mutations unique Spike enable enhanced entry into tissue. Unlike earlier SARS-CoV-2, our findings suggest enters independently serine transmembrane proteases instead relies upon metalloproteinases catalyze membrane fusion. Furthermore, demonstrate this pathway unlocked by enables evasion from constitutive interferon-induced antiviral factors restrict attachment. Therefore, transmissibility exhibited humans may be attributed not only its vaccine-elicited adaptive immunity, but also superior invasion epithelia resistance cell-intrinsic barriers present therein.

Язык: Английский

Процитировано

19
Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic DOI Creative Commons
Wilhelm Furnon, Vanessa M. Cowton, Giuditta De Lorenzo

и другие.

Nature Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Abstract SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging comprehensively compare many spikes that emerged during pandemic a single experimental platform. Here we generated panel recombinant viruses carrying different proteins from 27 circulating between 2020 and 2024 same genomic background. We then assessed several phenotypic traits both vitro vivo. found distinct among before after emergence Omicron variants. Spike post-Omicron maintained enhanced tropism for nasal epithelium large airways but displayed, over time, typical pre-Omicron Hence, with features pre- may continue emerge future.

Язык: Английский

Процитировано

2
The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5 DOI Creative Commons
Huiping Shuai, Jasper Fuk‐Woo Chan, Bingjie Hu

и другие.

EBioMedicine, Год журнала: 2023, Номер 95, С. 104753 - 104753

Опубликована: Авг. 12, 2023

Among the Omicron sublineages that have emerged, BA.1, BA.2, BA.5, and their related resulted in largest number of infections. While recent studies demonstrated all robustly escape neutralizing antibody response, it remains unclear on whether these share any pattern evolutionary trajectory replication efficiency intrinsic pathogenicity along respiratory tract.We compared virological features, capacity dominant BA.2 BA.5 human nasal epithelium, characterized K18-hACE2, A129, young C57BL/6, aged C57BL/6 mice.We found replicated most robustly, followed by differentiated epithelium. Consistently, infection higher viral gene copies, infectious titres more abundant antigen expression turbinates infected K18-hACE2 transgenic mice. In contrast, are continuously attenuated lungs mice, leading to decreased pathogenicity. Nevertheless, lung manifestations remain severe sublineages-infected A129 mice.Our results suggested might be gaining fitness upper tract, therefore highlighting importance global surveillance emergence hyper-transmissive sublineages. On contrary, is further lower tract. Effective vaccination other precautions should place prevent infections immunocompromised populations at risk.A full list funding bodies contributed this study can Acknowledgements section.

Язык: Английский

Процитировано

38
Evolution of the SARS-CoV-2 Omicron spike DOI Creative Commons
Ruth Parsons, Priyamvada Acharya

Cell Reports, Год журнала: 2023, Номер 42(12), С. 113444 - 113444

Опубликована: Ноя. 18, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern, first identified in November 2021, rapidly spread worldwide and diversified into several subvariants. spike (S) protein accumulated an unprecedented number sequence changes relative to previous variants. In this review, we discuss how S structural features modulate host cell receptor binding, virus entry, immune evasion highlight these differentiate from We also examine key properties track across the still-evolving subvariants importance continuing surveillance evolution over time.

Язык: Английский

Процитировано

35
Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination DOI Creative Commons
Xiaoyu Zhao, Tianyi Qiu, Xiner Huang

и другие.

Cell Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 6, 2024

Abstract The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging need to develop antivirals against related sarbecoviruses. Here, we identified both potent broadly neutralizing from a five-dose vaccinated donor who exhibited cross-reactive diverse coronaviruses. Through single B-cell sorting sequencing followed tailor-made computational pipeline, successfully selected 86 with potential cross-neutralizing ability 684 antibody sequences. Among them, PW5-570 potently neutralized that arose Omicron BA.5, other three could neutralize concern, SARS-CoV their sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, SHC014). Cryo-EM analysis demonstrates these have neutralization mechanisms, such as disassembling spike trimers, binding RBM SD1 affect ACE2 binding. In addition, prophylactic administration significantly protects nasal turbinate lung infections BA.1, XBB.1, viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment PW5-5 PW5-535 also markedly XBB.1 models. This study reveals utility process assist screening antibodies, well potency vaccine-induced sarbecoviruses, offering promising avenues for development broad therapeutic drugs.

Язык: Английский

Процитировано

15
Lineage-specific pathogenicity, immune evasion, and virological features of SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3 DOI Creative Commons

Yuanchen Liu,

Xiaoyu Zhao,

Jialu Shi

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 9, 2024

SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated immune resistance of but factors are speculated contribute global dominance, which remain elusive until today. Here, we find that a higher infectivity than in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, demonstrate gained over associates increased entry efficiency conferred by and better cleavage hNECs. Structurally, S455 altered mode binding protein ACE2 at

Язык: Английский

Процитировано

13
Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection DOI Creative Commons
Lei Yu,

Yajie Wang,

Yuanchen Liu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 7, 2024

Abstract Monoclonal antibody (mAb) therapeutics hold promise for both preventing and treating infectious diseases, especially among vulnerable populations. However, the emergence of various variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges current mAb treatments, emphasizing need more potent broadly neutralizing antibodies. In this study, we employed an unbiased screening approach to discover antibodies successfully isolated two mAbs from individuals with only exposure ancestral SARS-CoV-2. One these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum SARS-CoV-2 variants, including latest JN.1 KP.2 consistent IC 50 values ranging ∼1 5 ng/mL. Notably, it also displayed broad neutralization activity SARS-CoV related sarbecoviruses, such as WIV1, SHC014, RaTG13, GD-Pangolin. Structural analysis revealed that target shared hotspot but mutation-resistant epitopes, their Fabs locking RBD in “down” conformation through interactions adjacent RBDs, cross-linking Spike trimers into di-trimers block viral infection. vivo studies conducted JN.1-infected hamster model validated protective efficacy its therapeutic potential. These findings suggest that, meticulous approaches, rare activities sarbecoviruses can be identified exclusively virus exposure.

Язык: Английский

Процитировано

5
Lycium ruthenicum Murray derived exosome-like nanovesicles inhibit Aβ-induced apoptosis in PC12 cells via MAPK and PI3K/AKT signaling pathways DOI
Yadan Zhang, Xiaoyu Zhang, Tianhan Kai

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 277, С. 134309 - 134309

Опубликована: Июль 31, 2024

Язык: Английский

Процитировано

4