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

Zhenzhen Wang (), Shiqi Hu, Kristen D. Popowski, Shuo Liu, Dashuai Zhu, Xuan Mei, Junlang Li, Yilan Hu, Phuong-Uyen C. Dinh, Xiaojie Wang () and Ke Cheng ()
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Zhenzhen Wang: South China University of Technology, Guangzhou International Campus
Shiqi Hu: Columbia University, New York
Kristen D. Popowski: North Carolina State University
Shuo Liu: Columbia University, New York
Dashuai Zhu: Columbia University, New York
Xuan Mei: North Carolina State University
Junlang Li: Xsome Biotech Inc.
Yilan Hu: Columbia University, New York
Phuong-Uyen C. Dinh: North Carolina State University
Xiaojie Wang: Wenzhou Medical University
Ke Cheng: Columbia University, New York

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates its deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protects hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercepts the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and shows comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as a broad-spectrum protectant against existing and emerging virus variants.

Date: 2024
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DOI: 10.1038/s41467-024-45628-x

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