Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date. Angiotensin-converting enzyme 2 (ACE2) plays a fundamental role in SARS-CoV-2 pathogenesis because it allows viral entry into host cells. Here we show that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection. In mice, these LSC-nanodecoys were delivered via inhalation therapy and resided in the lungs for over 72 h post-delivery. Furthermore, inhalation of the LSC-nanodecoys accelerated clearance of SARS-CoV-2 mimics from the lungs, with no observed toxicity. In cynomolgus macaques challenged with live SARS-CoV-2, four doses of these nanodecoys delivered by inhalation promoted viral clearance and reduced lung injury. Our results suggest that LSC-nanodecoys can serve as a potential therapeutic agent for treating COVID-19.
【초록키워드】 COVID-19, SARS-CoV-2, Coronavirus disease 2019, ACE2, coronavirus, therapy, Infection, lung, Toxicity, Antiviral treatment, Lung injury, viral entry, viral clearance, global pandemic, mice, Lungs, human lung, therapeutic, SARS-CoV-2 pathogenesis, dose, cynomolgus macaque, host cells, acute respiratory syndrome, enzyme, live SARS-CoV-2, treating COVID-19, Host, Cell, neutralize, lung cell, PROTECT, caused, approved, reduced, accelerated, promoted, clearance of SARS-CoV-2, 【제목키워드】 COVID-19, SARS-CoV-2, Lung injury, non-human primate model, mitigate, neutralize,