한빛사 논문
Byoungjae Kong1, Seokoh Moon1, Yuna Kim1, Paul Heo1, Younghun Jung1, Seok-Hyeon Yu1, Jinhyo Chung1, Choongjin Ban1, Yong Ho Kim2, Paul Kim3, Beom Jeung wang3, Woo-Jae Chung1, Yeon-Kyun Shin4, Baik Lin Seong3 & Dae-Hyuk Kweon1,2,*
1 Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
2 Biomedical Institute for Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea.
3 Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
4 Department of Biochemistry Biophysics and Molecular Biology, Iowa State University, Iowa, IA 50011, USA.
These authors contributed equally: Byoungjae Kong, Seokoh Moon.
*Correspondence and requests for materials should be addressed to D.-H.K.
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.
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