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

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.