Research describes novel molecules designed to treat or prevent COVID-19 infection

Reviewed by Emily Henderson, B.Sc.Nov 6 2020

Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ: NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, today announced the publication in Science of research describing novel molecules designed to treat or prevent infection by the virus that causes COVID-19, SARS-CoV-2.

This report details the creation of de novo protein decoys that were specifically designed to bind the SARS-CoV-2 spike protein with high affinity, preventing its association with the viral receptor hACE2, which is required for infection. The manuscript titled "De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2" is available online here via Science First Release.

As reported, the optimized, hyper stable proteins act as decoys that bind to the virus and block cellular entry. The lead molecule, NL-CVX1 (CTC-445.2d), is shown to prevent infection of multiple human cell lines and to protect hamsters from serious consequences of SARS-CoV-2 infection.

Prophylactic intranasal administration of the protein decoy led to the survival of all hamsters challenged with a lethal dose of SARS-CoV-2.

"Our de novo proteins are designed to mimic the natural SARS-CoV-2 receptor, making them intrinsically resistant to viral mutation," said Daniel-Adriano Silva, Ph.D., Vice President Head of Research, who led the discovery effort at Neoleukin. "We believe the development of NL-CVX1 is the fastest development of a therapeutic de novo protein from concept to preclinical validation, and it represents our most sophisticated design to date."

The rapid development of this targeted protein demonstrates the potential of our de novo protein design platform and our team of scientists to address a broad spectrum of important biological problems."

Jonathan Drachman, MD, Chief Executive Officer, Neoleukin

"NL-CVX1 is designed to be stable and could potentially be administered by intranasal spray or inhalation to prevent and treat infection in the lungs and upper airways by SARS-CoV-2. We are currently evaluating the possibility of advancing this molecule to clinical trials in humans."