Journal
EMBO MOLECULAR MEDICINE
Volume 14, Issue 8, Pages -Publisher
WILEY
DOI: 10.15252/emmm.202115230
Keywords
COVID-19; treatment; clinical trial; vaccine
Categories
Funding
- T. von Zastrow foundation
- FWF Wittgenstein award [Z 271-B19]
- Austrian Academy of Sciences
- Innovative Medicines Initiative 2 Joint Undertaking (JU) [101005026]
- Canada 150 Research Chairs Program [F18-01336]
- Canadian Institutes of Health Research COVID-19 grants [F20-02343, F20-02015]
- European Union's Horizon 2020 research and innovation program
- EFPIA
- National Cancer Institute, National Institutes of Health [75N91019D00024, 75N91019F00130]
- Swiss National Science Foundation [P400PM_194473]
- Laulima Government Solutions, LLC
- US National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272201800013C]
- Swiss National Science Foundation (SNF) [P400PM_194473] Funding Source: Swiss National Science Foundation (SNF)
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The emergence of multiple SARS-CoV-2 variants has raised concerns due to reduced vaccine efficacy and resistance to neutralizing antibody therapies. However, research shows that soluble ACE2 can inhibit current SARS-CoV-2 variants, providing proof of principle for a pan-SARS-CoV-2 therapeutic.
The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic.
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