Related Experiment Video
Updated: Oct 20, 2025
Author Spotlight: Studying Host-Virus Interactions with Pseudotyped Viruses
Published on: November 21, 2023
Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles
Canhao Wu1,2, Qin Xu1, Huiyuan Wang2
1Artemisinin Research Center, First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou 510450, China.
Abstract:
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-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-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-CoV-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-CoV-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-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.
Insights
Extracellular vesicles engineered with decoy receptor ACE2 (EVs-ACE2) show promise in neutralizing SARS-CoV-2. Intranasal administration of EVs-ACE2 effectively blocked viral entry in mice, suggesting a potential preventive strategy for COVID-19.
Area of Science:
- Biotechnology
- Virology
- Drug Development
Background:
- The COVID-19 pandemic presents a significant global health challenge.
- Blocking the interaction between SARS-CoV-2 S protein and ACE2 is a key therapeutic target.
- Developing effective countermeasures against SARS-CoV-2 infection is urgently needed.
Purpose of the Study:
- To develop and evaluate a novel therapeutic strategy using extracellular vesicles (EVs) engineered with decoy angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 neutralization.
- To assess the efficacy of EVs-ACE2 in preventing viral entry both in vitro and in vivo.
Main Methods:
- Engineered cells were used to produce extracellular vesicles (EVs) stably expressing ACE2 (EVs-ACE2).
- In vitro neutralization assays were performed using S protein pseudoviruses (S-pseudovirus).
- In vivo studies involved intranasal administration of EVs-ACE2 in mice challenged with S-pseudovirus.
Main Results:
- EVs-ACE2 demonstrated the ability to inhibit S-pseudovirus infection across various cell types in vitro.
- Intranasal administration of EVs-ACE2 successfully suppressed S-pseudovirus entry into the mucosal epithelium in mice.
- The study confirmed the potential of EVs-ACE2 as a neutralizing agent against SARS-CoV-2.
Conclusions:
- Extracellular vesicles engineered with decoy ACE2 represent a promising strategy for SARS-CoV-2 neutralization.
- Intranasal EVs-ACE2 can serve as a preventive measure against SARS-CoV-2 infection by blocking viral entry.
- This EVs-based approach offers a potential new avenue for COVID-19 drug development.
