Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2
Authors: Monteil et al.
Journal/ Pre-Print: Journal pre-proof CellPress
Key Words: human recombinant soluble ACE2, kidney organoid, blood vessel organoids, treatment
1. Human recombinant soluble angiotensin-converting enzyme 2 (hrsACE-2) and not mouse recombinant soluble angiotensin converting enzyme 2 (msrACE-2) reduces SARS-CoV-2 infection of Vero-6 cells (kidney cell line) in a dose dependent manner
2. Human capillary organoids mimicking blood vessels in vivo can be infected by SARS-CoV-2 and serves as a host cell. Early phase of viral infection can be reduced by hrsACE2.
3. Kidney organoids express ACE2 and can be infected by SARS-CoV-2. Early phase of viral infection can be reduced by hrsACE2.
The study links hrsACE2 as a useful antiviral tool against SARS-CoV-2. The study uses SARS-CoV-2 isolated from a patient that successfully infects human capillary and kidney organoids. The supernatants from virus infected Vero-E6 cells and organoid cultures containing viral particles were able to re-infect these tissues. Clinical grade hrsACE2 reduces viral titre of SARS-CoV-2 in the engineered blood vessels and kidney tissues.
Impact for SARS-CoV2/COVID19 research efforts
For treatment of SARS-CoV2/COVID19 positive individuals
Study uses hrsACE2 to reduce infection and re-infection with SARS-CoV2 in the early stages of disease
· In vitro study
Strengths and limitations of the paper
Novelty: The study provides insights into the infection of SARS-CoV-2 at a cellular level where it interacts with the blood vessels and kidneys to establish infection.
Standing in the field: The study uses a previously trial tested drug hrsACE2 mentioned in literature. No controversial report
Appropriate statistics: Student’s t-tests have been used to measure significance between two treatment groups.
Viral model used: SARS-CoV2 strain isolated from a nasopharyngeal sample of a Swedish patient (Genbank accession number MT093571). The isolated strain was used to infect Vero-E6 cells, human capillary and kidney organoids.
Translatability: hrsACE2 has already been tested in phase I and II clinical trials (Haschke et al., 2013, Khan et al., 2017)
Main limitations: 1. Although novel, research was performed only on kidney and capillary organoids and not in primary lung epithelial cells or organoids.
2. Organoids as a model need a basement matrix to adhere and grow. Due to continuous proliferation of the stem cells the dead cells are released into the matrix. The model poses a limitation for determining toxicity as it would be difficult to differentiate if cell death is due to cellular proliferation or due to the drug. Data is not shown in the paper regarding toxicity.
3. The toxicity of hrsACE2 at higher concentrations is not shown. It is also unclear whether technical or experimental replicates were performed.
4. The early phase of the virus cycle was shown to be reduced by hrsACE2. It is not known how the drug would act during the late phase of the viral infection.
5. The authors declare conflict of interest as they are linked to Apeiron Biologics that holds a patent on the use of hrsACE2