Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2

Area of Science:

• Biotechnology
• Virology
• Pulmonology

Background:

• Emerging SARS-CoV-2 variants pose a significant threat to public health, necessitating novel therapeutic strategies.
• The interaction between the SARS-CoV-2 spike protein and the human ACE2 receptor is a critical step in viral infection.
• Developing therapeutics that inhibit this interaction is a promising approach to combat COVID-19.

Purpose of the Study:

• To investigate the potential of ACE2-expressing lung spheroid cell-derived exosomes (LSC-Exo) as a prophylactic agent against SARS-CoV-2 infection.
• To evaluate the efficacy of LSC-Exo in neutralizing SARS-CoV-2 and protecting against COVID-19-induced disease.

Main Methods:

• LSC-Exo were administered via inhalation to a mouse model to assess lung deposition and biodistribution.
• In vitro and in vivo studies were conducted to evaluate the ability of LSC-Exo to block SARS-CoV-2 interaction with host cells.
• Hamster models were used to assess the protective effects of LSC-Exo against SARS-CoV-2 infection and disease progression.
• The efficacy of LSC-Exo against SARS-CoV-2 variant pseudoviruses was tested in female mice.

Main Results:

• LSC-Exo demonstrated effective deposition and biodistribution throughout the lungs after inhalation in mice.
• LSC-Exo successfully neutralized SARS-CoV-2 in vitro and inhibited viral entry into host cells.
• LSC-Exo treatment protected hamsters from SARS-CoV-2-induced disease and significantly reduced viral loads.
• LSC-Exo showed broad-spectrum activity, neutralizing multiple SARS-CoV-2 variants and the wild-type strain.

Conclusions:

• LSC-Exo can serve as a prophylactic agent against SARS-CoV-2 infection by neutralizing the virus.
• LSC-Exo exhibits broad-spectrum efficacy against various SARS-CoV-2 strains, including emerging variants.
• Inhaled LSC-Exo represents a promising therapeutic strategy for preventing and treating COVID-19.