Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles  

作　　者：Canhao Wu Qin Xu Huiyuan Wang Bin Tu Jiaxin Zeng Pengfei Zhao Mingjie Shi Hong Qiu Yongzhuo Huang 

机构地区：[1]Artemisinin Research Center,First Clinical School,Guangzhou University of Chinese Medicine,Guangzhou 510450,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [3]Zhongshan Institute for Drug Discovery,SIMM,CAS,Zhongshan 528437,China [4]Center of Clinical Pharmacology,The Second Affiliated Hospital of Zhejiang University,School of Medicine,Hangzhou 310009,China [5]NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,Shanghai 201203,China [6]Taizhou University,School of Advanced Study,Institute of Natural Medicine and Health Product,Taizhou 318000,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第3期1523-1533,F0004,共12页药学学报（英文版）

基　　金：support of National Special Project for Significant Drugs Development(2018ZX09711002-010-002,China);National Natural Science Foundation of China(81925035 and 81521005,China);Shanghai Sci-Tech Innovation Initiative(19431903100,18430740800,China);the Shanghai Collaborative Innovation Group of Early Diagnosis and Precise Treatment of Hemangiomas and Vascular Malformations(SSMUZDCX20180701,China);the Sanofi-SIBS Yong Faculty Award,and The Youth Innovation Promotion Association;。

摘　　要：The spread of coronavirus disease 2019(COVID-19)throughout the world has resulted in stressful healthcare burdens and global health crises.Developing an effective measure to protect people from infection is an urgent need.The blockage of interaction between angiotensin-converting enzyme 2(ACE2)and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)drugs.A full-length ACE2 protein could be a potential drug to block early entry of SARS-Co V-2 into host cells.In this study,a therapeutic strategy was developed by using extracellular vesicles(EVs)with decoy receptor ACE2 for neutralization of SARS-Co V-2.The EVs embedded with engineered ACE2(EVs-ACE2)were prepared;the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression.The potential effect of the EVs-ACE2 on anti-SARS-Co V-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein(S-pseudovirus).EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells,and importantly,the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium.Therefore,the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-Co V-2 infection.This EVs-based strategy offers a potential route to COVID-19 drug development.

关 键 词：SARS-CoV-2 COVID-19 Spike protein PSEUDOVIRUS Extracellular vesicles ACE2 Intranasal administration NEUTRALIZATION 

分 类 号：R914[医药卫生—药物化学]