A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex.
bioRxiv
; 2022 Jul 19.
Article
en En
| MEDLINE
| ID: mdl-34931190
ABSTRACT
We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. One Sentence Summary:
A host-targeted drug to treat all respiratory viruses without viral resistance development.
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1
Banco de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
BioRxiv
Año:
2022
Tipo del documento:
Article