Dana-Farber scientists have developed a medication that neutralises SARS-CoV-2, the COVID-19 coronavirus, and every other tested version. The medicine is developed so that natural selection maintains its activity against future viral strains.
The investigational medicine is not an antibody but an ACE2 receptor decoy, according to a research in Science Advances. Unlike antibodies, the SARS-CoV-2 virus cannot evade the ACE2 decoy because changes that would allow it to do so would impair its capacity to infect cells. Dana-Farber scientists figured out how to make this medicine more potent in COVID-19-infected animals and safe for patients.
This report comes as the antibody medicines used to treat COVID-19 have lost their potency due to an altered viral spike protein.
The researchers uncovered traits that made ACE2 decoys powerful and long-lasting. The collectrin-like domain of the ACE2 protein made the medication cling more securely to the virus and last longer in the body. ACE2 decoys exhibit significant efficacy against the COVID-19 virus because they pop the viral spike protein so it can’t attach to the cell-surface ACE2 receptors and attack cells.
Spike proteins allow SARS-CoV-2 to infect cells. The spike protein attaches to the cell’s ACE2 receptor and refolds, allowing the viruses to enter. ACE2 decoys pop the virus before it can enter cells by luring it to attach to the decoy instead of the cell. This explains the drug’s potency: it’s a competitive inhibitor and permanently downregulates the virus. Versions can alter, but they must continue to attach to ACE2 for infection; hence, the medicine is active against all variants.
The medicine disclosed in this study could be used to treat novel coronaviruses that could infect humans in the future. Many coronaviruses that could infect humans employ ACE2 to infect cells.
DF-COV-01 has not yet been tried in humans, but manufacturing development is virtually complete, and preclinical investigations are continuing for regulatory approval.
This work was supported by a CDMRP Technology/Therapeutic Development Award. The National Institutes of Health, Evergrande MassCPR, and COVID-19 FastGrants contributed additional funding.
