Polypeptides for managing viral infections
Inventors
George, Sanil • Jacob, Joshy • Holthausen, David • Lee, Song Hee • Shartouny, Jessica
Assignees
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Publication Number
US-11666630-B2
Publication Date
2023-06-06
Expiration Date
Abstract
Antiviral polypeptides and methods of use are provided herein. In particular, these polypeptides can comprise the Yodha amino acid sequence, variants, derivatives, or truncated versions thereof. In certain embodiments, this disclosure relates to uses of the peptides, nucleic acid molecules, and compositions disclosed herein to treat or prevent a viral infection.
Core Innovation
The invention relates to isolated polypeptides defined by one of specified amino acid sequences, including polypeptides consisting of the amino acid sequence (SEQ ID NO:1) SMLLLFFLGTISLSLCQDDQERC, (SEQ ID NO:56) SMLLLFFLGTISLSLCQ, (SEQ ID NO:57) PMLLLFFLGTISLSLCQ, or (SEQ ID NO:65) LLFFLGTISLSLCQDDQERC. The disclosed polypeptides are derived from a frog host-defense peptide referred to as Yodha (Hylarana aurantiaca), and are presented as antiviral polypeptides.
A key feature is that the polypeptide is acetylated or amidated. The disclosure further describes variant or truncation rules and homologous variants of the Yodha-based sequence, where sequence-identity thresholds and patterns of substitution, insertion, deletion, and length limits are used to define related polypeptides.
The invention addresses the treatment or prevention of viral infections by providing pharmaceutical compositions comprising the acetylated or amidated Yodha-based polypeptides and, in some cases, additional antiviral compounds. The documented polypeptide activity is described as virucidal against multiple Zika virus strains, with reductions in infectivity/viral titers and reduced viral entry into cells, and electron microscopy evidence of virion disruption.
Claims Coverage
The independent claim covers isolated acetylated or amidated polypeptides defined by multiple specified amino-acid sequences, with inventive claim elements centered on sequence selection and terminal acetylation or amidation. Dependent claims extend coverage to pharmaceutical compositions and further refine the formulation types and inclusion of additional antivirals.
Isolated polypeptide defined by specified sequences
An isolated polypeptide consisting of the amino acid sequence of (SEQ ID NO:1) SMLLLFFLGTISLSLCQDDQERC, (SEQ ID NO:56) SMLLLFFLGTISLSLCQ, (SEQ ID NO:57) PMLLLFFLGTISLSLCQ, or (SEQ ID NO:65) LLFFLGTISLSLCQDDQERC.
Acetylated or amidated terminal modification
The polypeptide is acetylated or amidated.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition comprising an effective amount of the polypeptide together with a pharmaceutically acceptable carrier.
Composition including an additional antiviral compound
The pharmaceutical composition further includes an additional antiviral compound.
Dosage-form selection among multiple solid formats
The composition is in the form of a capsule, tablet, pill, powder, granule, or gel.
Sterilized pH-buffered aqueous salt solution formulation
The composition is specifically in the form of a sterilized pH-buffered aqueous salt solution.
Overall, the claim set ties the antiviral polypeptide definition to specific sequence variants of the Yodha-derived peptide and requires acetylation or amidation, while dependent claims extend the scope to pharmaceutical compositions using a pharmaceutically acceptable carrier, optional additional antivirals, and specific formulation formats including multiple solid dosage forms and a sterilized pH-buffered aqueous salt solution.
Stated Advantages
Virucidal activity against multiple Zika virus strains, with reductions in infectivity/viral titers.
Reduced viral entry into cells and virion disruption evidenced by electron microscopy.
Non-toxicity to human red blood cells (RBCs) and activity of both L- and D-forms.
Activity of naturally occurring homologous variants and increased activity for certain variants/truncations.
Virucidal activity extending to dengue virus serotypes.
Virucidal activity against influenza, including activity related to HA binding.
Reductions in mouse viremia/burden.
Documented Applications
Treating or preventing viral infections, including Zika virus, dengue virus (serotypes DENV 1-4), influenza, and HIV.
Use in pharmaceutical compositions formulated with pharmaceutically acceptable carriers, including enteric-coated solids and sterilized pH-buffered aqueous salt solutions, as well as sprays/propellant containers and combination therapy with additional antiviral compounds.
Use in formulations that include nucleic acids encoding the peptides and vaccine compositions.
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