PEPTIDES THAT INHIBIT INFECTION BY SARS-COV-2, THE VIRUS THAT CAUSES COVID-19 DISEASE

Smart overview of the Invention

The patent application describes polypeptide compounds designed to inhibit the infectivity of the SARS-CoV-2 virus, responsible for COVID-19. These compounds, termed anti-SARS-CoV-2 α/β-polypeptides, are incorporated into pharmaceutical compositions aimed at treating and ameliorating infections in mammals, including humans. The invention was developed with support from the National Institutes of Health, reflecting its potential significance in public health.

Technical Background

SARS-CoV-2 is an enveloped virus that requires the fusion of its membrane with the host cell membrane to initiate infection. This process is mediated by the Spike protein, which undergoes conformational changes to form a stable six-helix bundle (6HB) structure, facilitating membrane fusion. Similar mechanisms are employed by other viruses like HIV, where drugs such as Enfuvirtide inhibit infection by blocking 6HB formation. However, these drugs often face challenges like rapid degradation in the bloodstream, necessitating frequent dosing.

Innovation and Solution

The disclosed polypeptides incorporate non-natural β-amino acid residues, enhancing their resistance to proteolysis and improving pharmacological activity. By modifying the peptide backbone with β-amino acids, the susceptibility to protease cleavage is significantly reduced. These polypeptides are modeled on the HR2 domain of the CoV2 Spike protein and are potent inhibitors of the viral fusion process.

Composition and Variants

The invention includes various embodiments of the polypeptides, where α-amino acid residues are replaced with β-amino acids, some of which may be cyclically constrained. These modifications enhance the stability and solubility of the peptides. Additionally, the polypeptides can be conjugated with lipid or poly(ethylene glycol) moieties to further improve their therapeutic properties. Cholesterol, tocopherol, and palmitate are among the lipid moieties that can be attached to these peptides.

Applications and Benefits

The application proposes methods for using these compositions to inhibit SARS-CoV-2 infection and ameliorate symptoms in humans. This includes administering a pharmaceutical composition containing the polypeptides, potentially offering a more stable and effective treatment option. The disclosed invention represents a promising advancement in antiviral therapeutics, with the potential to improve treatment outcomes for COVID-19 patients.