The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2). This virus gains entry to host cells via ACE2, which is expressed by
type 2 alveolar epithelial cells in the lungs and by cells in other tissues, including
the heart, kidney and blood vessels. Researchers now show that SARS-CoV-2 can infect
human blood vessel and kidney organoids and that this infection can be inhibited by
human recombinant soluble ACE2 (hrsACE2).
To assess whether hrsACE2 — a decoy protein that has already been tested in phase
I and II clinical trials — can inhibit the interaction between SARS-CoV-2 and ACE2,
Josef Penninger, Ali Mirazimi, Nuria Montserrat and colleagues administered the recombinant
protein to SARS-CoV-2-infected Vero E6 cells. Treatment of cells with hrsACE2 inhibited
SARS-CoV-2 infection in a dose-dependent manner and attenuated propagation of the virus.
Based on the hypothesis that the presence of ACE2 in extrapulmonary tissues might
explain the multi-organ dysfunction caused by COVID-19, the researchers developed
human capillary organoids from induced pluripotent stem cells, and kidney organoids
from human embryonic stem cells. “Importantly, single-cell RNA sequencing of the kidney
organoids showed that ACE2 is expressed in different cell populations, including tubular-like
cells and podocyte-like cells,” says Montserrat. Following infection of the organoids
with SARS-CoV-2 the researchers could detect viral RNA that increased in the days
following infection, indicative of viral replication. Addition of hrsACE2, however,
again reduced SARS-CoV-2 levels in a dose-dependent manner. “Our findings not only
suggest that tissue organoids can be used to study the effects of SARS-CoV-2 on extrapulmonary
tissues, but also suggest that rhsACE2 might block the virus from entering target
cells,” says Penninger.