Decoy receptor protects against Omicron infection

Osaka, Japan - They say that the best defense is a good offense; and now, researchers from Japan have found that the best defense against coronavirus disease 2019 (COVID-19) infection could be a good decoy.

In a recently published study, researchers from Osaka University and Kyoto Prefectural University of Medicine have revealed that a specially designed ‘decoy’ virus receptor reduces the infectivity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant in cells and experimental animal models.

Most current treatments for SARS-CoV-2 infection involve antibodies that have been designed to neutralize the virus. However, the effectiveness of these antibodies varies depending on the virus variant, and the virus can rapidly develop mutations that help it ‘escape’ neutralization. An alternative strategy is to use decoys that imitate the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2). With this approach, the virus binds to the ACE2 decoy instead of to cells expressing the actual ACE2 protein, so the virus never comes into contact with or enters the cells.

“By engineering small mutations into ACE2, we were able to improve its affinity for the spike protein of SARS-CoV-2, to the point where it was able neutralize the virus just as well as therapeutic antibodies do,” says Atsushi Hoshino, senior author on the study. “However, the Omicron variant of SARS-CoV-2 has many new mutations in the spike protein, so we wanted to know whether our engineered ACE2 was also effective in preventing infection with this variant.” To do this, the researchers infected cells with different variants of SARS-CoV-2 and treated them with the engineered ACE2 decoy.

“The results were very clear,” explains Hoshino. “The engineered ACE2 effectively neutralized the Omicron variant of SARS-CoV-2, to a level comparable to that seen with the original Wuhan variant.”

In addition, treating hamsters or mice with the engineered ACE2 protected them from Omicron, resulting in less severe infection and improved chance of survival.

“Our findings suggest that ACE2 is a useful therapeutic option for treating a wide variety of SARS-CoV-2 variants, including Omicron,” explains Hoshino.

Furthermore, a detailed analysis of the mutations found in the Omicron variant is highly unlikely to ‘escape’ neutralization by the ACE2 decoy, unlike the virus’s tendency to rapidly evade neutralization by antibody-based treatments. Given that the engineered ACE2 was also able to neutralize other viruses related to SARS-CoV-2 that typically infect animals, it is possible that this strategy could also be beneficial for managing future disease outbreaks.

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The article, “An engineered ACE2 decoy neutralizes the SARS-CoV-2 Omicron variant and confers protection against infection in vivo,” was published in Science Translational Medicine at DOI: https://doi.org/10.1126/scitranslmed.abn7737

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan's most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Website: https://resou.osaka-u.ac.jp/en

About Kyoto Prefectural University of Medicine

In 2022, Kyoto Prefectural University of Medicine will be 150 years since the hospital that has developed into our present organization was founded. Moreover 2021, saw the 100th anniversary of the issuance of our university title. The riches of our university are however not limited to being one of Japan’s few medical schools with a long history and tradition.

Fundamental to our university is the education of professionals who have advanced specialized knowledge and respond to developments in medicine and care. In addition to the education of nurses and doctors, we continue to develop the curriculum of our graduate school, and foster our cooperation with the government and local enterprises.

Website: https://www.kpu-m.ac.jp/doc/english/index.html