Methods and compositions for treating infections
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.
1. A compound having the formula:
(Peptide-Linker) n -B-Hydrophobic Moiety
wherein said Peptide is a non-native C-terminus heptad repeat region (HRC) Peptide that comprises the sequence of:
(SEQ ID NO. 2)
dIdGdSdIdD NASVVN I QKE I DRLNEV A KN L NES L IDLQEL,
wherein the dIdGdSdIdD represents that the first five amino acids of said sequence are in the D-configuration;
said Linker is a bivalent linking moiety,
B is a multivalent moiety and n is an integer selected from 1, 2, and 3.
2. The compound of claim 1 , wherein the Hydrophobic moiety is cholesterol.
3. A method for the treatment of a disease associated with severe acute respiratory syndrome coronavirus type 2 (SARS-COV-2) infection in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of the compound of claim 2 .
4. The method of claim 3 , wherein the administration is achieved using an inhaler or a nebulizer.
5. The compound of claim 1 , wherein the Linker comprises a flexible peptide.
6. The compound of claim 1 , wherein the Linker comprises a polyethyleneglycol.
7. The compound of claim 1 , wherein n is 2.