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  • Virucidal nano-perforator of viral membrane trapping viral RNAs in the endosome.

Virucidal nano-perforator of viral membrane trapping viral RNAs in the endosome.

Nature communications (2019-01-16)
Byoungjae Kong, Seokoh Moon, Yuna Kim, Paul Heo, Younghun Jung, Seok-Hyeon Yu, Jinhyo Chung, Choongjin Ban, Yong Ho Kim, Paul Kim, Beom Jeung Hwang, Woo-Jae Chung, Yeon-Kyun Shin, Baik Lin Seong, Dae-Hyuk Kweon
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Mouse IgG (whole molecule)–Peroxidase antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Avanti
Syringe (250 μL), Avanti Research - A Croda Brand
Sigma-Aldrich
Anti-GT1b Ganglioside Antibody, ascites fluid, clone GT1b-2b, Chemicon®
Avanti
Ganglioside-Total, Avanti Research - A Croda Brand
Avanti
27-hydroxycholesterol (D6), Avanti Research - A Croda Brand