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1.
Protein Cell ; 15(2): 121-134, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37470320

RESUMO

Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs (bnAbs) and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two angiotensin-converting enzyme 2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing. Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5. Together, these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Microscopia Crioeletrônica , Anticorpos Neutralizantes , Anticorpos Antivirais
2.
Virology ; 574: 1-8, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35858511

RESUMO

HIV-1 remains one of the most devastating infectious pathogens without available vaccines. A valid neutralization assay using multiple representative virus strains is prerequisite for antibody response analysis in HIV-1 vaccine development, where HIV pseudoviruses (PsVs) commonly serve as surrogate agents for the authentic HIV, offering a safer manipulation in Biosafety Level 2+. However, PsV production is of low efficiency and is unstable in this field. Here, we optimize PsV production conditions via the use of alternative host cells, packaging ratios and gene truncation. We show that a 153-aa truncation of the endodomain substantially enhances the packaging efficiency of HIV PsVs, providing 4 to 25 times higher infection titers than the full-length Env. Further, we obtained a robust HIV-1 PsV panel covering 12 representative global strains for neutralization assay testing. This work sheds light on how to optimize HIV PsV packaging, and provides functional insight into the cytoplasmic domain of HIV-1.


Assuntos
Infecções por HIV , HIV-1 , Anticorpos Neutralizantes , Anticorpos Anti-HIV , HIV-1/genética , Humanos , Testes de Neutralização
3.
Carbohydr Res ; 339(4): 873-9, 2004 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-14980831

RESUMO

The Ugi four-component reaction (U-4CR) was utilized to prepare divalent and trivalent cluster mannosides with different scaffolds. The glycoclusters obtained were tested for their relative inhibitory potency against the binding of yeast mannan to concanavalin A by solid-phase enzyme-linked lectin assays (ELLA) using methyl alpha-D-mannopyranoside as a standard. Among them, a divalent mannoside containing aromatic groups showed the strongest binding affinity to concanavalin A.


Assuntos
Concanavalina A/antagonistas & inibidores , Mananas/antagonistas & inibidores , Manosídeos/síntese química , Manosídeos/farmacologia , Leveduras/química , Concanavalina A/metabolismo , Mananas/metabolismo , Manosídeos/química , Estrutura Molecular , Ligação Proteica/efeitos dos fármacos
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