Targeting COVID-19 Variants to Stop Infection Before It Begins

What you need to know

In a study supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID), researchers have made progress on a new type of treatment for variants of SARS-CoV-2, the virus that causes COVID-19. In early studies, mice treated with a specially engineered protein had fewer COVID-19 symptoms and were more likely to survive.

What did the researchers do?

A protein called angiotensin-converting enzyme 2 (ACE2) sits on the surface of cells. When SARS-CoV-2 enters our bodies, spike proteins on the virus stick to ACE2. This is the first step of infection.

To stop infection before it even begins, researchers have been studying ways to stop the virus from ever attaching to ACE2. One option may be a “decoy” protein — a lab-engineered ACE2 lookalike that binds to the virus particles before they can reach the cell surface.

Researchers treated mice with this decoy ACE2 and then exposed the mice to either the original virus or the Gamma variant of SARS-CoV-2. Other mice were exposed to the virus without being treated with the decoy protein.

The results showed that mice treated with the decoy ACE2 had fewer symptoms of COVID-19 and were less likely to die of the disease, whether the infection came from the original virus or the Gamma variant. This indicates that ACE2 can be engineered to help prevent both the original virus and SARS-CoV-2 variants from successfully sticking to and infecting living cells.

Why is this research important?

Since the original strain, SARS-CoV-2 has mutated several times, creating viral variants. Some of these variants are different enough from the original virus that they do not respond to existing treatments.

Although this research focused on only the original SARS-CoV-2 and the Gamma variant, other research on the use of decoy ACE2 proteins found that it was also effective against the Alpha, Beta, and Delta variants. Further research into the use of decoy ACE2 may include the development of treatments that work against these and future variants, potentially saving lives.

Where can I go to learn more?

“Decoy” Protein Works Against Multiple Coronavirus Variants in Early Study

• Dr. Lawrence Tabak talks more about this research in the NIH Director’s Blog.

COVID-19 Treatments

• NIH has information and FAQs about available COVID-19 treatments.

Finding Effective Treatments for SARS-CoV-2 Variants

• A different NIAID study looked at monoclonal antibody treatments for SARS-CoV-2 variants.

Sources

Zhang, L., Dutta, S., Xiong, S., Chan, M., Chan, K. K., Fan, T. M., Bailey, K. L., Lindeblad, M., Cooper, L. M., Rong, L., Gugliuzza, A. F., Shukla, D., Procko, E., Rehman, J., & Malik, A. B. (2022). Engineered ACE2 decoy mitigates lung injury and death induced by SARS-CoV-2 variants. Nature Chemical Biology, 18, 342–351. https://doi.org/10.1038/s41589-021-00965-6