Lysosomal “TRAP”: a neotype modality for clearance of viruses and variants

Chengliang Lyu, Zhanlong He, Xiaoming Hu, Shuang Wang, Meng Qin, Li Zhu, Yanyan Li, Fengmei Yang, Zhouguang Jiao, Xiao Zhang, Guihong Lu, Erqiang Wang, Yaling Hu, Yu Zhai, Youchun Wang, Weijin Huang, Dongshu Wang, Yimin Cui, Xiaocong Pang, Xiangzheng Liu, Hidehiro Kamiya, Guanghui Ma () and Wei Wei ()
Additional contact information
Chengliang Lyu: Chinese Academy of Sciences
Zhanlong He: Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease
Xiaoming Hu: Chinese Academy of Sciences
Shuang Wang: Chinese Academy of Sciences
Meng Qin: Beijing University of Chemical Technology
Li Zhu: Beijing Institute of Biotechnology
Yanyan Li: Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease
Fengmei Yang: Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease
Zhouguang Jiao: Chinese Academy of Sciences
Xiao Zhang: Chinese Academy of Sciences
Guihong Lu: Chinese Academy of Sciences
Erqiang Wang: Ltd.
Yaling Hu: Ltd.
Yu Zhai: Ltd.
Youchun Wang: National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals
Weijin Huang: National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals
Dongshu Wang: Beijing Institute of Biotechnology
Yimin Cui: Peking University First Hospital
Xiaocong Pang: Peking University First Hospital
Xiangzheng Liu: Peking University First Hospital
Hidehiro Kamiya: Tokyo University of Agriculture and Technology
Guanghui Ma: Chinese Academy of Sciences
Wei Wei: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract The binding of viruses to host-entry factor receptors is an essential step for viral infection. Many studies have shown that macrophages can internalize viruses and degrade them in lysosomes for clearance in vivo. Inspired by these natural behaviors and using SARS-CoV-2 as a testbed, we harvest lysosomes from activated macrophages and anchor the protein-receptor ACE2 as bait, thus constructing a lysosomal “TRAP” (lysoTRAP) that selectively captures, internalizes, and eventually degrades SARS-CoV-2. Through experiments with cells, female mice, female hamsters, and human lung organoids, we demonstrate that lysoTRAP effectively clears SARS-CoV-2. Importantly, unlike therapeutic agents targeting SARS-CoV-2 spike protein, lysoTRAP remains effective against nine pseudotyped variants and the authentic Omicron variant, demonstrating its resistance to SARS-CoV-2 mutations. In addition to the protein-receptor ACE2, we also extend lysoTRAP with the saccharide-receptor sialic acid and verify its excellent antiviral effect against H1N1, highlighting the flexibility of our “TRAP” platform in fighting against various viruses.

Date: 2024
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DOI: 10.1038/s41467-024-54505-6

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