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-10898544-B2
Publication Date
2021-01-26
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 and compositions disclosed herein to treat or prevent a viral infection.
Core Innovation
The patent describes the host-defense peptide "Yodha" comprising the amino acid sequence SMLLLFFLGTISLSLCQDDQERC (SEQ ID NO: 1), and related polypeptides comprising specific amino acid sequences including SMLLLFFLGTISLSLCQ (SEQ ID NO: 56), PMLLLFFLGTISLSLCQ (SEQ ID NO: 57), and LLFFLGTISLSLCQDDQERC (SEQ ID NO: 65), for antiviral and virucidal activity. The described peptides include variants/derivatives with sequence identity to the referenced sequences, including short/truncated peptides and motif-based forms.
The described embodiments further include optional chemical modifications of the polypeptides, including amidation and acetylation, and use of D-amino acid (D-enantiomer) forms, together with stabilizing caps/moieties as described. The document also describes delivery and composition concepts including pharmaceutical compositions with a carrier, vaccine composition and/or adjuvant formulations, and recombinant vector/expression system concepts for administration.
The patent describes the problem of treating viral infections and provides a method for treating a viral infection in a subject in need thereof by administering an effective amount of a polypeptide comprising one of the specified Yodha sequences. The disclosed use includes antiviral activity against multiple envelope viruses, including Zika virus (ZIKV), dengue virus (DENV), influenza viruses, and HIV, and also includes embodiments involving additional antiviral compounds such as oseltamivir in combination.
Claims Coverage
The independent claim provides coverage for treating a viral infection in a subject by administering an effective amount of a polypeptide with one of several specified amino acid sequences. The dependent claim set refines the targeted viruses and narrows additional treatment aspects such as additional antiviral compounds and specific polypeptide chemical modifications.
Administering an effective amount of a specified Yodha polypeptide sequence
Treating a viral infection in a subject by administering an effective amount of a polypeptide comprising the amino acid sequence SMLLLFFLGTISLSLCQDDQERC (SEQ ID NO: 1), a polypeptide comprising the amino acid sequence SMLLLFFLGTISLSLCQ (SEQ ID NO: 56), a polypeptide comprising the amino acid sequence PMLLLFFLGTISLSLCQ (SEQ ID NO: 57), or a polypeptide comprising the amino acid sequence LLFFLGTISLSLCQDDQERC (SEQ ID NO: 65).
Treating a Zika virus infection
The method is performed for a Zika virus infection.
Combination with oseltamivir
Administering an additional antiviral compound, specifically oseltamivir, to the subject.
Amidated or acetylated polypeptide
The polypeptide is amidated or acetylated.
Overall, the claim coverage centers on antiviral treatment using defined Yodha-derived polypeptide sequences, with further refinements to Zika infection, optionally combining with oseltamivir, and optionally using amidated or acetylated polypeptides.
Stated Advantages
Selectively reduces ZIKV infectivity/replication.
Disrupts ZIKV virions.
Shows non-toxicity to human RBCs, with a reported IC50.
Inhibits multiple ZIKV strains.
Reduces viral burden in mice.
Neutralizes/virucidally acts against dengue serotypes.
Acts against multiple influenza subtypes.
Truncation variants retain activity.
Documented Applications
Preventing or treating viral infections in a subject by administering Yodha polypeptides, including antiviral and virucidal activity against envelope viruses such as Zika virus, dengue virus, influenza viruses, and HIV.
Applications include treating Zika virus infection.
Combination use with an additional antiviral compound, specifically oseltamivir.
Formulation concepts including pharmaceutical compositions with a carrier, and vaccine composition/adjuvant formulations and recombinant vector/expression system concepts.
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