Anti-SARS-CoV-2 immunoadhesin remains effective against Omicron and other emerging variants of concern

• Published in: iScience Vol. 25; no. 10; p. 105193
• Main Authors: Cohen-Dvashi, Hadas, Weinstein, Jonathan, Katz, Michael, Eilon-Ashkenazy, Maayan, Mor, Yuval, Shimon, Amir, Achdout, Hagit, Tamir, Hadas, Israely, Tomer, Strobelt, Romano, Shemesh, Maya, Stoler-Barak, Liat, Shulman, Ziv, Paran, Nir, Fleishman, Sarel Jacob, Diskin, Ron
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.10.2022; The Authors; Elsevier
• Subjects: Biological sciences; Health sciences; Immunology; Virology; Health sciences; Biological sciences; Immunology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105193

Blocking the interaction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with its angiotensin-converting enzyme 2 (ACE2) receptor was proved to be an effective therapeutic option. Various protein binders as well as monoclonal antibodies that effectively target the receptor-binding domain (RBD) of SARS-CoV-2 to prevent interaction with ACE2 were developed. The emergence of SARS-CoV-2 variants that accumulate alterations in the RBD can severely affect the efficacy of such immunotherapeutic agents, as is indeed the case with Omicron that resists many of the previously isolated monoclonal antibodies. Here, we evaluate an ACE2-based immunoadhesin that we have developed early in the pandemic against some of the recent variants of concern (VoCs), including the Delta and the Omicron variants. We show that our ACE2-immunoadhesin remains effective in neutralizing these variants, suggesting that immunoadhesin-based immunotherapy is less prone to escape by the virus and has a potential to remain effective against future VoCs. [Display omitted] •ACE2-based immunoadhesins are a promising therapeutic tool against SARS-CoV-2•We employed a computational approach to design a superior ACE2 binder•An order of magnitude increase in neutralization capacity compared with human ACE2•The modified ACE2 retains efficacy against emerging variants of concern Health sciences; Virology; Immunology; Biological sciences.