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

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

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2 Citations (Scopus)

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.

Original languageEnglish
Article number185
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Kong, B., Moon, S., Kim, Y., Heo, P., Jung, Y., Yu, S. H., Chung, J., Ban, C., Kim, Y. H., Kim, P., Hwang, B. J., Chung, W. J., Shin, Y. K., Seong, B. L., & Kweon, D. H. (2019). Virucidal nano-perforator of viral membrane trapping viral RNAs in the endosome. Nature communications, 10(1), [185]. https://doi.org/10.1038/s41467-018-08138-1