Development of a two-component recombinant vaccine for COVID-19 DOI Creative Commons
Yisheng Sun, Fang Xu,

Han-Ping Zhu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Дек. 20, 2024

Though COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues pose significant threat human society. Vaccination remains one most effective methods for preventing COVID-19. While antigenic regions are found in receptor binding domain (RBD), N-terminal (NTD) S protein is another crucial region inducing neutralizing antibodies (nAbs) against

Язык: Английский

DIONYSUS: a database of protein–carbohydrate interfaces DOI Creative Commons
Aria Gheeraert,

Thomas Bailly,

Yani Ren

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 53(D1), С. D387 - D395

Опубликована: Окт. 22, 2024

Protein-carbohydrate interactions govern a wide variety of biological processes and play an essential role in the development different diseases. Here, we present DIONYSUS, first database protein-carbohydrate interfaces annotated according to structural, chemical functional properties both proteins carbohydrates. We provide exhaustive information on nature interactions, binding site composition, function specific additional retrieved from existing databases. The user can easily search using protein sequence structure or by carbohydrate properties. Moreover, for given interaction site, perform its comparison with representative subset non-covalent retrieve potential specificity. Therefore, DIONYSUS is source valuable deeper understanding general patterns, annotation previously unannotated such applications as carbohydrate-based drug design. freely available at www.dsimb.inserm.fr/DIONYSUS/.

Язык: Английский

Процитировано

4

A cost-effective approach for comprehensive analysis of human memory B Cell repertoire: fast isolation of broad neutralizing mAbs to SARS-CoV-2 variants DOI Creative Commons
Luciana Conde, Débora L. Oliveira, Gabriela Maciel

и другие.

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

Опубликована: Янв. 16, 2025

Abstract The SARS-CoV-2 pandemic highlighted the urgent need for innovative methods to study humoral immune responses and identify monoclonal antibodies (mAbs) with diagnostic therapeutic potential. Memory B cells (MBCs), pivotal adaptive immunity, generate high-affinity upon antigen re-encounter. While single-cell high-throughput sequencing has revolutionized antibody repertoire studies, it critical limitations: inability simultaneously determine antigen-binding specificities immunoglobulin gene sequences, high resource demands that limit accessibility in low-resource settings. Here, we present a cost-effective culture (SCC) platform enabling comprehensive analysis of human MBC repertoires, including epitope-specific responses, cross-reactivity mAb isolation. Using convalescent vaccinated donor samples, optimized SCCs NB21 feeder cells, R848, IL-2 stimulation, achieving cloning efficiency 30-fold enrichment antigen-specific MBCs compared bulk cultures. Among 592 isolated mAbs, 52.7% exhibited specificity Wuhan strain Spike protein, 27.9% targeting receptor-binding domain (RBD), 15.4% N-terminal (NTD), 56.7% other regions, likely S2 domain. Comparative revealed distinct patterns: 40.5% all anti-Spike mAbs recognized tested variants (Wuhan, Beta, Delta, Gamma Omicron BA.2), while 29.6% showed recognition only four variants, majority not BA.2; 56 single reactive (14.9%) were also identified. Notably, screening neutralization assays performed directly supernatants, eliminating large-scale transfection. Desired clones selected recombinant production. SCC enabled unbiased profiling, revealing convergent V-region rearrangements, public V3-30 V3-53/V3-66 consistent prior studies. Two RBD-targeting broad potential validated pseudovirus assays. This streamlined delivers simultaneous isolation, sequencing, functional studies within seven days, empowering researchers settings address global health inequities enhance preparedness future pandemics.

Язык: Английский

Процитировано

0

A Structural Voyage Toward the Landscape of Humoral and Cellular Immune Escapes of SARSCoV‐2 DOI Open Access

Jun Liu,

Yan Wu, George F. Gao

и другие.

Immunological Reviews, Год журнала: 2025, Номер 330(1)

Опубликована: Фев. 5, 2025

ABSTRACT The genome‐based surveillance of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in the past nearly 5 years since its emergence has refreshed our understanding virus evolution, especially on convergent co‐evolution with host. SARS‐CoV‐2 evolution been characterized by sets mutations that affect functional properties altering infectivity, virulence, transmissibility, and interactions host immunity. This poses a huge challenge to global prevention control measures based drug treatment vaccine application. As one key evasion strategies response immune profile human population, there are overwhelming amounts evidence for reduced antibody neutralization variants. Additionally, data also suggest levels CD4 + CD8 T‐cell responses against variants or sub‐variants decrease populations, although non‐negligible cross‐T‐cell maintained. Herein, from perspectives structural immunology, we outline characteristics mechanisms T cell SARS‐CoV variants/sub‐variants. molecular bases impact escaping interaction epitopes receptors adaptive immunity, is, major histocompatibility complex (MHC), receptor (TCR), summarized discussed, knowledge which will widen this pandemic‐threatening assist preparedness Pathogen X future.

Язык: Английский

Процитировано

0

Conformational dynamics of the HIV-1 envelope glycoprotein from CRF01_AE is associated with susceptibility to antibody-dependent cellular cytotoxicity DOI Creative Commons
Marco A. Díaz-Salinas, Debashree Chatterjee, Manon Nayrac

и другие.

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

Опубликована: Авг. 22, 2024

The HIV-1 envelope glycoprotein (Env) is expressed at the surface of infected cells and as such can be targeted by non-neutralizing antibodies (nnAbs) that mediate antibody-dependent cellular cytotoxicity (ADCC). Previous single-molecule Forster resonance energy transfer (smFRET) studies demonstrated Env from clinical isolates predominantly adopt a 'closed' conformation (State 1), which resistant to nnAbs. After interacting with receptor CD4, conformational equilibrium shifts toward States 2 3, exposing coreceptor binding site (CoRBS) permitting targeting this site. We showed anti-CoRBS Abs enables engagement other nnAbs target cluster A epitopes on Env. Anti-cluster stabilize an asymmetric conformation, State 2A, have potent ADCC activity. CRF01_AE strains were suggested intrinsically susceptible mediated This may due presence histidine position 375, known shift towards more 'open' conformations. In work, through adaptation established smFRET imaging approach, we report dynamics native, unliganded HIV-1CRF01_AE indicates frequent sampling 2A conformation. in striking contrast Envs clades B, for example HIV-1JR-FL, do not transition absence ligands. These findings inform Env, are relevant structure-based design both synthetic inhibitors binding, enhancers therapeutic alternatives.

Язык: Английский

Процитировано

2

Phytonutrient Formulation Using Gum Arabic and Adansonia Digitata Pulp: Lessons for Boosting the Human Immune System - Part 1 DOI Creative Commons
Ahmed A. M. Elnour,

Nour Hamid Abdurahman

Phytomedicine Plus, Год журнала: 2024, Номер unknown, С. 100663 - 100663

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

0

Multi-step shapeshifting of SARS-CoV-2 Omicron spikes during fusion DOI
Xu Wang, Yang Han, Maolin Lu

и другие.

Structure, Год журнала: 2024, Номер 32(11), С. 1850 - 1851

Опубликована: Ноя. 1, 2024

Язык: Английский

Процитировано

0

Computational Insights into Acrylamide Fragment Inhibition of SARS-CoV-2 Main Protease DOI Creative Commons
Ping Chen, Liyuan Wu, Bo Qin

и другие.

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(11), С. 12847 - 12865

Опубликована: Ноя. 12, 2024

The pathogen of COVID-19, SARS-CoV-2, has caused a severe global health crisis. So far, while COVID-19 been suppressed, the continuous evolution SARS-CoV-2 variants reduced effectiveness vaccines such as mRNA-1273 and drugs Remdesivir. To uphold prior to potential coronavirus outbreaks, it is necessary explore underlying mechanisms between biomolecules nanodrugs. experimental study reported that acrylamide fragments covalently attached Cys145, main protease enzyme (Mpro) occupied substrate binding pocket, thereby disrupting dimerization. However, mechanism linking them unclear. purpose this work complement validate results, well facilitate novel antiviral drugs. Based on our studies, we identified two constructed corresponding protein-ligand complex models. Subsequently, performed molecular dynamics (MD) simulations unveil crucial interaction these nanodrugs Mpro. This approach allowed capture various conformations both monomeric dimeric Mpro, revealing significant conformational dissociation catalytic helix domains, which indicates presence allosteric targets. Notably, Compound 5 destabilizes Mpro dimerization acts an effective inhibitor by specifically targeting active site, resulting in enhanced inhibitory effects. Consequently, can modulate Mpro’s equilibrium among extended monomeric, compact, forms, shedding light small molecules inhibitors against coronaviruses. Overall, research contributes broader understanding drug development fragment-based approaches covalent therapeutics.

Язык: Английский

Процитировано

0

Cellular sialoglycans are differentially required for endosomal and cell-surface entry of SARS-CoV-2 in lung cell lines DOI Creative Commons

Kimberley C. Siwak,

Emmanuelle V. LeBlanc,

Heidi M. Scott

и другие.

PLoS Pathogens, Год журнала: 2024, Номер 20(12), С. e1012365 - e1012365

Опубликована: Дек. 3, 2024

Cell entry of severe acute respiratory coronavirus-2 (SARS-CoV-2) and other CoVs can occur via two distinct routes. Following receptor binding by the spike glycoprotein, membrane fusion be triggered cleavage either at cell surface in a transmembrane serine protease 2 (TMPRSS2)-dependent manner or within endosomes cathepsin-dependent manner. Cellular sialoglycans have been proposed to aid CoV attachment entry, although their functional contributions each pathway are unknown. In this study, we used genetic enzymatic approaches deplete sialic acid from surfaces compared requirement for during endosomal cell-surface using lentiviral particles pseudotyped with proteins different sarbecoviruses. We show that SARS-CoV-1, WIV1-CoV WIV16-CoV, like SARS-CoV-2 omicron variant, depends on cathepsins requires cellular entry. Ancestral delta variant use but only require cells lacking TMPRSS2. Binding protein did not acid, nor was required TMRPSS2-expressing cells. These findings suggest strictly attachment, fusion, rather promote endocytic related contrast, MERS-CoV pseudoparticles authentic HCoV-OC43 affected TMPRSS2 expression, consistent described role merbecovirus embecovirus attachment. Overall, these clarify mediate endosomal, cell-surface,

Язык: Английский

Процитировано

0

Development of a two-component recombinant vaccine for COVID-19 DOI Creative Commons
Yisheng Sun, Fang Xu,

Han-Ping Zhu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Дек. 20, 2024

Though COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues pose significant threat human society. Vaccination remains one most effective methods for preventing COVID-19. While antigenic regions are found in receptor binding domain (RBD), N-terminal (NTD) S protein is another crucial region inducing neutralizing antibodies (nAbs) against

Язык: Английский

Процитировано

0