Researchers from Northwestern University, the University of Washington, and Washington University at St. Louis have published data demonstrating that select miniproteins neutralized SARS-CoV-2 better than mAbs currently in use for the treatment of COVID-19. The multivalent minibinder demonstrated potent activity against all variants of the virus tested, including Delta and Omicron, and is expected to be effective against future variants.
According to the article published in Science Translational Medicine, intranasally administered minibinders protected well against infection in a challenge study in human ACE2-expressing transgenic mice and “results indicate that intranasal administration of TRI2-1 or TRI2-2 confer protection against SARS-CoV-2 infection as both pre-exposure prophylaxis and post-exposure therapy in a stringent model of disease.”
Michael Jewett, Professor of Chemical and Biological Engineering at Northwestern University explains, “SARS-CoV-2’s spike protein has three binding domains, and common antibody therapies may only block one. Our minibinders sit on top of the spike protein like a tripod and block all three. The interaction between the spike protein and our antiviral is among the tightest interactions known in biology. When we put the spike protein and our antiviral therapeutic in a test tube together for a week, they stayed connected and never fell apart. To enter the body, the spike protein and ACE2 receptor engage in a handshake. Our antiviral blocks this handshake and, as a bonus, has resistance to viral escape.”
The authors of the article conclude that the minibinders’ “small size and stability may enable direct nebulization into the human upper respiratory tract, a strategy that could increase accessibility for patients over the typical intravenous or subcutaneous routes used for administering neutralizing mAbs.” A press release from Northwestern noted that the minibinder nasal spray is being advanced into Phase 1 trials.
Read the Northwestern University press release.
Read the Science Translational Medicine article.
