journal article·2024-04-01

Heparin-Conjugated ACE2-Bearing Extracellular Vesicles As Engineered Dual-Decoy for Combating the SARS-CoV-2 Omicron Variant via Pulmonary Delivery

Bin Tu, Zhenzhen Pan, Huiyuan Wang, Jingkun Qu, Feifei Sun, Mingjie Shi, Yingyan Zhang, Han Wu, Bahtiyor Muhitdinov, Yongzhuo Huang

ACS Materials Letters· Volume 6· Issue 4
Publisher page

Abstract

The very highly contagious Omicron variant of SARS-CoV-2, repeated infection, and long COVID symptoms continue to be a health threat with few convenient preventive or therapeutic methods suitable for common use. Spike-glycan interactions play an essential role in SARS-CoV-2 infections, and heparan sulfate acts as a coreceptor for mediating the cell entry of the virus. In response to this challenge, we proposed a dual-decoy strategy using both heparin (an analogue of heparan sulfate) and ACE2 to neutralize SARS-CoV-2. We developed a heparin-conjugated ACE2-bearing extracellular vesicle system (haEVs), serving as nano dual bait, with high efficiency in neutralizing the Omicron variant through interactions with the viral Spike protein. In vitro experiments showed that haEVs bound to the pseudovirus of SARS-CoV-2 and effectively prevented the pseudovirus infection of host cells. In vivo experiments further demonstrated that inhalable haEVs effectively blocked the pseudovirus infection of lung tissue of the Omicron variant with good biosafety. This dual-decoy approach presents a promising avenue for combating SARS-CoV-2, especially the Omicron variant, with the advantage of self-administration for preventive and therapeutic applications.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · SARS-CoV-2 and COVID-19 Research · MXene and MAX Phase Materials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

University of Chinese Academy of Sciences, Beijing 100049, China

Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528437, China

Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

Experimental Teaching Center, Guangxi University of Chinese Medicine, Nanning 530200, China

School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China

School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310024, China

Laboratory Animal Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, 83 M. Ulughbek Street, Tashkent 100125, Uzbekistan

NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, Shanghai 201203, China

Funding

Guangdong Provincial Department of Science and Technology · Zhongshan Science and Technology Bureau · Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences · National Key Research and Development Program of China · Sanofi · Youth Innovation Promotion Association of the Chinese Academy of Sciences · National Natural Science Foundation of China

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