Scytovirin domain 1 related polypeptides
Inventors
O'Keefe, Barry R. • Xiong, Chang-yun • McMahon, James B. • Byrd, Andrew
Assignees
US Department of Health and Human Services
Publication Number
US-8067530-B2
Publication Date
2011-11-29
Expiration Date
2026-05-24
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Abstract
A scytovirin domain 1 (SD1) polypeptide, a nucleic acid encoding the polypeptide, and related fusion proteins, conjugates, isolated cells, vectors, and antibodies, as well as a method of inhibiting a viral infection using the same.
Core Innovation
The invention provides new antiviral polypeptides, nucleic acids encoding these polypeptides, fusion proteins, conjugates, isolated cells, vectors, and antibodies related to a scytovirin domain 1 (SD1) polypeptide. It also offers methods of inhibiting a viral infection using these compositions. The invention focuses on polypeptides comprising amino acid sequences that have 65% or greater sequence identity to SEQ ID NO: 1, excluding SEQ ID NO: 4, which is the full scytovirin polypeptide sequence.
The polypeptides of the invention, derived from a portion of scytovirin (SD1, amino acids 1-48), retain biological properties similar to the full scytovirin polypeptide, including the ability to bind viral proteins such as gp41 or gp120 of immunodeficiency viruses (e.g., HIV) and exhibiting antiviral activity comparable to or greater than scytovirin. The invention encompasses variants and fragments maintaining antiviral activity, nucleic acids encoding these polypeptides, antibodies targeting them, and fusion proteins or conjugates incorporating them.
The background describes the problem of viral infections, particularly HIV/AIDS, which remain a challenging cause of morbidity and mortality worldwide, with limited effective preventions or therapies. There exists an urgent global need for new effective preventative and therapeutic agents against HIV/AIDS and other lethal viral diseases. The invention addresses this need by providing novel polypeptides and related compositions derived from scytovirin that can inhibit viral infections through binding to viral envelope glycoproteins and inducing antiviral effects.
Claims Coverage
The claims disclose seven main inventive features related to isolated polypeptides derived from SEQ ID NO: 1, their conjugates, and compositions including these polypeptides.
Isolated polypeptide comprising SEQ ID NO: 1
An isolated or purified polypeptide that comprises the amino acid sequence of SEQ ID NO: 1 (scytovirin domain 1).
Polypeptide comprising linked SEQ ID NO: 1 sequences by flexible spacer
A polypeptide comprising the amino acid sequence of SEQ ID NO: 1 linked via a flexible spacer to a second amino acid sequence of SEQ ID NO: 1.
Polypeptide comprising albumin
A polypeptide comprising the amino acid sequence of SEQ ID NO: 1 fused with albumin.
Conjugate comprising the polypeptide of SEQ ID NO: 1
A conjugate that includes the polypeptide of claim 1, potentially including additional effector components.
Conjugate with effector components
A conjugate as above further comprising one or more effector components selected from polyethylene glycol, dextran, an antiviral agent, or a solid support matrix.
Composition comprising polypeptide and carrier
A composition containing the polypeptide of claim 1 together with a carrier, excipient, or adjuvant.
Isolated polypeptide comprising SEQ ID NO: 2
An isolated or purified polypeptide comprising the amino acid sequence of SEQ ID NO: 2, a preferred sequence related to the invention.
The claims cover isolated polypeptides encompassing SEQ ID NO: 1 and SEQ ID NO: 2, their fusion forms including linkers and albumin, conjugates with effector components, and pharmaceutical compositions containing these polypeptides. These features focus on SD1-derived sequences and their functional derivatives for antiviral use.
Stated Advantages
The invention provides polypeptides with antiviral activity comparable to or greater than scytovirin.
D-form amino acid polypeptides improve retention of biological activity in vivo by resisting protease degradation.
Fusion proteins and conjugates can facilitate purification, targeting, or enhance stability and half-life.
Use of transformed nonpathogenic bacteria such as lactobacilli as delivery vehicles enables prolonged local antiviral activity, especially for female-controlled prophylaxis.
The compounds can inhibit viral infections therapeutically and prophylactically, including binding HIV envelope glycoproteins and inhibiting virus in biological samples or on inanimate objects.
Documented Applications
Inhibition of viral infections in a host, particularly HIV-1 and HIV-2, through administration of polypeptides, fusion proteins, conjugates, antibodies, nucleic acids, isolated cells, or compositions thereof.
Prophylactic and therapeutic use for preventing or treating viral infections, including topical administration to prevent sexual transmission of viruses such as HIV.
Use of antibodies to induce an immune response against viruses in a host.
Delivery of antiviral agents via genetically engineered commensal bacteria, particularly lactobacilli, to maintain antiviral activity on mucosal surfaces such as vaginal mucosa.
Ex vivo or in situ inhibition of virus in biological samples (e.g., blood, semen, tissues) or on inanimate objects (e.g., medical equipment surfaces) by contacting with polypeptides, fusion proteins, or conjugates of the invention.
Use in formulations suitable for various administration routes including oral, inhalation, transdermal, rectal, vaginal, and parenteral administration.
Possible incorporation into contraceptive devices such as condoms, diaphragms, cervical caps, vaginal rings, or sponges for delivering antiviral activity.
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