A robust high-throughput fluorescent polarization assay for the evaluation and screening of SARS-CoV-2 fusion inhibitors.
Bioorg Chem
; 116: 105362, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34598089
ABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a serious threat to global health. One attractive antiviral target is the membrane fusion mechanism employed by the virus to gain access to the host cell. Here we report a robust protein-based fluorescent polarization assay, that mimicking the formation of the six-helix bundle (6-HB) process during the membrane fusion, for the evaluation and screening of SARS-CoV-2 fusion Inhibitors. The IC50 of known inhibitors, HR2P, EK1, and Salvianolic acid C (Sal-C) were measured to be 6.1 nM, 2.5 nM, and 8.9 µM respectively. In addition, we found Sal-A has a slightly lower IC50 (3.9 µM) than Sal-C. Interestingly, simple caffeic acid can also disrupt the formation of 6-HB with a sub-mM concentration. Pilot high throughput screening (HTS) of a small marine natural product library validates the assay with a Z' factor close to 0.8. We envision the current assay provides a convenient way to screen SARS-CoV-2 fusion inhibitors and assess their binding affinity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Peptídeos
/
Alcenos
/
Ensaios de Triagem em Larga Escala
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Polifenóis
/
Polarização de Fluorescência
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article