Virucidal nano-perforator of viral membrane trapping viral RNAs in the endosome.
Nat Commun
; 10(1): 185, 2019 01 14.
Article
en En
| MEDLINE
| ID: mdl-30643128
ABSTRACT
Membrane-disrupting agents that selectively target virus versus host membranes could potentially inhibit a broad-spectrum of enveloped viruses, but currently such antivirals are lacking. Here, we develop a nanodisc incorporated with a decoy virus receptor that inhibits virus infection. Mechanistically, nanodiscs carrying the viral receptor sialic acid bind to influenza virions and are co-endocytosed into host cells. At low pH in the endosome, the nanodiscs rupture the viral envelope, trapping viral RNAs inside the endolysosome for enzymatic decomposition. In contrast, liposomes containing a decoy receptor show weak antiviral activity due to the lack of membrane disruption. The nanodiscs inhibit influenza virus infection and reduce morbidity and mortality in a mouse model. Our results suggest a new class of antivirals applicable to other enveloped viruses that cause irreversible physical damage specifically to virus envelope by viruses' own fusion machine. In conclusion, the lipid nanostructure provides another dimension for antiviral activity of decoy molecules.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
2_enfermedades_transmissibles
/
6_other_respiratory_diseases
Asunto principal:
Antivirales
/
Virus de la Influenza A
/
ARN Viral
/
Permeabilidad de la Membrana Celular
/
Gripe Humana
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2019
Tipo del documento:
Article