Methods and compositions for treating infections
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Publication Number
US-12226474-B2
Publication Date
2025-02-18
Expiration Date
Abstract
The invention provides a compound comprising one, two, three or more non-natural HRC sequence of a viral spike peptide conjugated to a hydrophobic moiety via an optional linker. The hydrophobic moiety can be a membrane integrating ligand, such as a cholesterol, a sphingolipid, a glycolipid, a glycerophospholipid. The non-natural viral spike peptide is preferably a coronavirus spike protein characterized by one or more D-amino acids. The peptides of the invention inhibit viral fusion. The invention includes compositions for the delivery of compounds of the invention, such as pulmonary or nasal delivery. The invention also provides a method of treating or preventing a viral infection, including for example a SARS-COV-2 (COVID-19) infection, in a subject in need thereof comprising administering an effective amount of a compound of the invention.
Core Innovation
The invention relates to compositions and treatment methods for viral respiratory infections using conjugates that comprise non-natural coronavirus spike HRC peptides. The compositions include a Peptide-Linker conjugated to a membrane-integrating hydrophobic moiety, and the described peptide is a non-native C-terminus heptad repeat region (HRC) peptide, including Retro-Inversion (RI) HRC peptides.
The conjugates are linked by an optional linker, which can be bivalent and is associated with multivalent moieties, including n selected from 1, 2, and 3. The conjugate is described using a formula of (Peptide-Linker)n-B-Hydrophobic Moiety, where the hydrophobic moiety includes cholesterol and other lipid moieties such as sphingolipid, glycolipid, or glycerophospholipid.
The compositions are described for pulmonary or nasal delivery, including inhalation, nebulizer, and aerosol delivery, and are administered in an amount effective to treat or prevent infections. The documented mechanism is viral fusion inhibition involving the HRC/HRN fusion region, and the treatment context includes respiratory infections such as SARS-CoV-2 (COVID-19).
Claims Coverage
The independent claim recites a peptide-linker-hydrophobic moiety conjugate defined by a non-native HRC peptide sequence, an optional D-configuration feature, and a linker/multivalency structure. The provided excerpt also includes method-focused coverage for treatment of SARS-CoV-2-associated disease and delivery via inhaler or nebulizer routes.
Non-native C-terminus heptad repeat region peptide with d-configuration
A compound where the peptide is a non-native C-terminus heptad repeat region (HRC) peptide comprising the sequence of SEQ ID NO. 2 with dIdGdSdIdD indicating that the first five amino acids of the sequence are in the D-configuration.
Bivalent linker with multivalency and defined n
A compound where the linker is a bivalent linking moiety and B is a multivalent moiety, with n being an integer selected from 1, 2, and 3 in the formula (Peptide-Linker)n-B-Hydrophobic Moiety.
Overall, the claim coverage centers on a conjugate architecture that combines a non-native C-terminal HRC peptide sequence with an encoded D-configuration feature, together with a bivalent linker and a multivalent presentation defined by n (1–3), linked to a membrane-integrating hydrophobic moiety.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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