Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.
Level 5 - mechanism / opinion, no new human data
In vitro cell culture and human organoid bench study
PubMed 32333836 · doi:10.1016/j.cell.2020.04.004
What was done
Researchers tested the ability of clinical-grade human recombinant soluble ACE2 (hrsACE2) and mouse recombinant soluble ACE2 to block SARS-CoV-2 infection. Efficacy was evaluated in Vero cell cultures and in engineered human blood vessel and human kidney organoids.
What was found
Clinical-grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000 to 5,000. In contrast, equivalent mouse rsACE2 showed no inhibitory effect. SARS-CoV-2 directly infected engineered human blood vessel organoids and human kidney organoids, and this infection was inhibited by hrsACE2 (quantitative values for organoid inhibition were not reported in the abstract).
Why it matters
The study provides preclinical proof-of-concept that clinical-grade soluble ACE2 can act as a decoy receptor to block early-stage SARS-CoV-2 infection across cell cultures and complex human organoids.
Limits
The study is restricted to cell culture and tissue-engineered organoid models; it provides no in vivo pharmacokinetics, animal model efficacy, or clinical human safety and outcome data. Quantitative reduction metrics, sample sizes, and dosing parameters for the organoid experiments are not detailed in the abstract.
Cited by
- supports A study found that human recombinant soluble ACE2 reduced SARS-CoV-2 infection in engineered human organoid tissues.