Conserved role of spike S2 domain N-glycosylation across betacoronaviruses

npj Viruses, Год журнала: 2025, Номер 3(1)

Опубликована: Янв. 25, 2025

Abstract Besides acting as an immunological shield, the N-glycans of SARS-CoV-2 are also critical for viral life cycle. As S2 subunit spike is highly conserved across betacoronaviruses, we determined functional significance five ‘stem N-glycans’ located in between N1098-N1194. Studies were performed with 31 Asn-to-Gln mutants, betacoronavirus virus-like particles and single-cycle replicons. Deletions stem enhanced S1 shedding from trimeric spike, reduced ACE2 binding abolished syncytia formation. When three or more deleted, expression on cell surface incorporation into virions was both reduced. Viral entry function progressively lost upon deleting N1098 glycan combination additional glycosite modifications. In addition to SARS-CoV-2, SARS-CoV MERS-CoV prevented target cells. These data suggest multiple roles N-glycans, evolutionarily properties these complex carbohydrates human betacoronaviruses.

Язык: Английский

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Pseudotyped Viruses: A Useful Platform for Pre-Clinical Studies Conducted in a BSL-2 Laboratory Setting

Biomolecules, Год журнала: 2025, Номер 15(1), С. 135 - 135

Опубликована: Янв. 15, 2025

The study of pathogenic viruses has always posed significant biosafety challenges. In particular, the highly requires methods with low biological risk but relatively high sensitivity and convenience in detection. recent years, pseudoviruses, which consist a backbone one virus envelope proteins another virus, have become most widely used tools for exploring mechanisms binding to cells, membrane fusion viral entry, as well screening libraries antiviral substances, evaluating potential neutralizing monoclonal antibodies, developing neutralization tests, therapeutic platforms. During outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pseudotyped virus-based assays played pivotal role advancing our understanding virus-cell interactions its disease pathogenesis. Such facilitated search agents accelerated epidemiological studies on post-infection post-vaccination humoral immunity. This review focuses use pseudoviruses model large-scale applications enveloped viruses.

Язык: Английский

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SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

The immune response to viral infection is shaped by past exposures related virus strains, a phenomenon known as imprinting. For SARS-CoV-2, much of the population has been imprinted spike from an early strain, either through vaccination or during stages COVID-19 pandemic. As consequence this imprinting, with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited imprinting strain. Here we compare neutralizing antibody specificities individuals versus infants infected Specifically, use pseudovirus-based deep mutational scanning measure how mutations affect neutralization serum adults and children original vaccine primary XBB* variant. While activity targets receptor-binding domain (RBD), only mostly N-terminal (NTD). In these infants, secondary exposure via shifts towards RBD, although specific RBD sites targeted are different than for adults. dramatic differences in among histories likely impact evolution.

Язык: Английский

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Development of antiviral drugs for COVID-19 in 2025: unmet needs and future challenges

Expert Review of Anti-infective Therapy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

The success in the COVID-19 pandemic containment largely originated from vaccine- and infection-elicited immunity, with SARS-CoV-2 infection only marginally mitigated by availability of antiviral drugs. current lack effective prophylactic therapeutic agents immunocompromised patients highlights need for a radical change design both drug manufacturing clinical trials. In this review authors summarize their suggestions manufacturers, reviewing classes small molecule antivirals passive immunotherapies highlighting limitations unexploited potential. Molecular serological testing can improve appropriateness. Efficacy be improved combining different while preserving economical sustainability. Respiratory delivery should better investigated

Язык: Английский

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Multiple Exposures to SARS-CoV-2 Spike enhance Cross-Reactive Antibody-Dependent Cellular Cytotoxicity against SARS-CoV-1

Virology, Год журнала: 2025, Номер 607, С. 110512 - 110512

Опубликована: Март 22, 2025

Язык: Английский

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SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

ABSTRACT The immune response to viral infection is shaped by past exposures related virus strains, a phenomenon known as imprinting. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), much of the population has been imprinted spike from an early strain, either through vaccination or during stages COVID-19 pandemic. As consequence this imprinting, with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited imprinting strain. Here we compare neutralizing antibody specificities individuals versus infants infected Specifically, use pseudovirus-based deep mutational scanning measure how mutations affect neutralization serum adults and children original vaccine primary XBB* variant. While activity targets receptor-binding domain (RBD), only mostly N-terminal domain. In these infants, secondary exposure via shifts toward RBD, although specific RBD sites targeted are different adults. dramatic differences in among histories likely impact evolution. IMPORTANCE We show that person’s history strongly affects which regions on their target. particular, who have just once strain make target than exposed both older strains. This person-to-person heterogeneity means same mutation can impacts immunity people.

Язык: Английский

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Regional Dynamics and Mechanisms Behind SARS-CoV-2 XDV.1 Prevalence in Chongqing via Genomic Surveillance and Molecular Insights

Virus Research, Год журнала: 2025, Номер unknown, С. 199562 - 199562

Опубликована: Март 1, 2025

Язык: Английский

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Anti-S2 antibodies responsible for the SARS-CoV-2 infection-induced serological cross-reactivity against MERS-CoV and MERS-related coronaviruses

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 28, 2025

Sarbecoviruses, such as SARS-CoV-2, utilize angiotensin-converting enzyme 2 (ACE2) the entry receptor; while merbecoviruses, MERS-CoV, use dipeptidyl peptidase 4 (DPP4) for viral entry. Recently, several MERS-related coronaviruses, NeoCoV and PDF-2180, were reported to ACE2, same receptor enter cells, raising possibility of potential recombination between SARS-CoV-2 coronaviruses within co-infected ACE2-expressing cells. However, facing this risk, serum antibody cross-reactivity against MERS/MERS-related after vaccination and/or infection is still elusive. Here, in study, we showed that serological S proteins could be induced by but not inactivated vaccination. Further investigation revealed due monoclonals recognizing relatively conserved S2 epitopes, fusion peptide stem helix, antibodies receptor-binding domain (RBD), N-terminal (NTD) or subdomain-1 (SD1). Some these anti-S2 cross-reactive mAbs cross-neutralizing activity, none them exhibited antibody-dependent enhancement (ADE) effect vitro. Together, results dissected infection-induced highlighted significance region design development pan-β-coronaviruses vaccines.

Язык: Английский

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Entry Efficiency, Protease Dependence, and Antibody-Mediated Neutralization of SARS-CoV-2 Sublineages KP.3.1.1 and XEC

Vaccines, Год журнала: 2025, Номер 13(4), С. 385 - 385

Опубликована: Апрель 3, 2025

Background: The SARS-CoV-2 variants KP.3.1.1 and XEC currently dominate the COVID-19 epidemic. However, their cell tropism, proteolytic processing, susceptibility to neutralization by monoclonal antibodies remain incompletely characterized. Methods: We employed pseudotyped viruses assess entry efficiency of in various lines, dependence on TMPRSS2 for lung entry, ability use ACE2 infection. Additionally, we evaluated BD55-4637 BD55-5514. Results: entered lines with similar as parental JN.1 lineage utilized Calu-3 entry. Unlike JN.1, failed efficiently murine Both were effectively neutralized BD55-5514, suggesting therapeutic potential. Conclusions: Our findings demonstrate that KP.3.1.1, XEC, like predecessor BA.2.86, rely sensitive certain neutralizing antibodies. these differ utilize species orthologs

Язык: Английский

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Structure and function of an unusual R452-dependent monoclonal antibody against SARS-CoV-2

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) variants is still a major public health concern worldwide. Currently, SARS-CoV-2 have been widely used to develop the updated vaccine. However, whether these mutated residues good immunogenicity remains elusive. In particular, we know little about what kind of antibodies can be induced infection or vaccination and their biological characteristics. Here, identified an R452-dependent monoclonal neutralizing antibody, ConD-852, from primarily Delta variant-infected individual, indicating that R452 residue has immunogenicity. We determined high-resolution cryo-electron microscopy (cryo-EM) structure ConD-852 complexed with receptor-binding domain (RBD), revealing how it binds R452-related epitopes detailed interactions. Interestingly, could only bind amino acid “R” at 452 position on RBD, displaying strict restriction recognize SARS-CoV-2. Overall, our findings regarding confirmed carrying L452R mutation enriched knowledge binding model involving antibody virus. IMPORTANCE Although update COVID-19 vaccine candidate, mutations unknown. This study demonstrates induce potent reports cryo-EM around RBD.

Язык: Английский

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