Cell-mimicking nanodecoys neutralize SARS-CoV-2 and mitigate lung injury in a non-human primate model of COVID-19

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.

Cytokine-scavenging nanodecoys reconstruct osteoclast/osteoblast balance toward the treatment of postmenopausal osteoporosis

“…Recently, cell membrane–coated nanodecoys have shown great promise for cytokine/antibody clearance and toxin neutralization through interactions with membrane proteins ( 36 – 39 ). These cell membrane–coated nanodecoys that inherit the antigenic profile of the source cell can absorb and neutralize pathological molecules ( 37 , 40 – 42 ).…”

Nanoagent-based theranostic strategies against human coronaviruses

“…To theoretically optimize this antiviral nanoformulation, they used molecular docking and dissipative particle dynamics (DPD) simulations to computationally investigate the drug-carrier interactions and their assembly process. They verified the strong interactions between Dnase-1-coated PD-PEG NPs 220 Suppress neutrophil activities and cytokine storm [106] Nanodepot of manganese (Mn 2+ ) 35 Release Mn 2+ to promote IFN response [111] Abbreviations. PD-PEG: polydopamine-poly(ethylene glycol); Dnase-1: deoxyribonuclease I; PAMAM: polyamidoamine.…”

Application of Nanomaterials as an Advanced Strategy for the Diagnosis, Prevention, and Treatment of Viral Diseases

“…Nanodecoys enable customization with various types of cellular vesicle components. Li et al reported that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) neutralized COVID-19 and mitigated lung injury [178]. Furthermore, LSC-nanodecoys promoted viral clearance and reduced lung injury via inhalation administration.…”