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-8481255-B2
Publication Date
2013-07-09
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 a scytovirin domain 1 (SD1) polypeptide comprising an amino acid sequence with 65% or greater sequence identity to SEQ ID NO: 1, excluding the full scytovirin polypeptide sequence SEQ ID NO: 4. The SD1 polypeptide is derived from amino acids 1-48 of scytovirin and retains biological properties similar to scytovirin, such as binding viral proteins (e.g., gp41 or gp120 of HIV) and exhibiting antiviral activity against HIV and other viruses.
The invention further encompasses fusion proteins and conjugates comprising the SD1 polypeptide, nucleic acids encoding the polypeptide, isolated cells containing such nucleic acids, and antibodies binding specifically to the SD1 sequence or its variants. These biological molecules and compositions can be used in methods to inhibit viral infections by administering viral infection-inhibiting amounts of these compounds or by contacting biological samples or inanimate objects with them.
The problem addressed by the invention is the pressing need for new effective preventative and therapeutic agents against viral infections such as HIV/AIDS, for which existing vaccinations and therapies have proven insufficient. The invention aims to provide novel polypeptides and proteins derived from scytovirin with potent antiviral properties to fill this unmet need.
Claims Coverage
The claims cover methods of inhibiting viral infection in hosts and in biological samples or inanimate objects using polypeptides and related compositions comprising the amino acid sequence of SEQ ID NO: 1, along with further embodiments enhancing efficacy and applications.
Use of SD1 polypeptide to inhibit viral infection in hosts
A method of inhibiting infection of a host by a virus having a glycoprotein comprising a high mannose oligosaccharide as a surface protein, comprising administering a virus-inhibiting amount of a polypeptide including the amino acid sequence SEQ ID NO: 1, targeting oligomannose-8, oligomannose-9, or a combination thereof.
Combination therapy with additional antiviral substances
The method optionally includes prior, simultaneous, or subsequent administration of a substance other than the SD1 polypeptide that is efficacious in inhibiting the viral infection, enhancing therapeutic outcomes.
Targeting immunodeficiency viruses, especially HIV
The method specifically applies to immunodeficiency viruses, including human immunodeficiency virus (HIV), with the host being a human.
Enhanced polypeptide structures
The SD1 polypeptide can be modified to include flexible spacers linking two SEQ ID NO: 1 sequences or can be fused to albumin to improve properties.
Use of SD1 polypeptides in conjugates
The SD1 polypeptide can be part of a conjugate further comprising one or more effector components such as polyethylene glycol, dextran, antiviral agents, or solid support matrices to improve stability, delivery, or targeting.
Inhibition of virus in biological samples or inanimate objects
Methods of contacting biological samples or inanimate objects with virus-inhibiting amounts of the SD1 polypeptide to inhibit viruses comprising high mannose oligosaccharides on surface glycoproteins.
Further combination treatments in ex vivo contexts
Contacting biological samples or inanimate objects can be combined with other substances efficacious in inhibiting the virus, in prior, simultaneous, or subsequent manners.
The claims focus on the use of the SD1 polypeptide and derivatives for inhibiting viruses, particularly HIV, through administration to hosts or by contact with biological samples or objects, with enhancements including fusion proteins, conjugates, and combination therapies to optimize viral inhibition.
Stated Advantages
The polypeptide SD1 has antiviral activity comparable to or greater than the full scytovirin protein, enabling effective viral inhibition.
The invention provides a smaller polypeptide domain that retains binding specificity to viral proteins gp120 and gp41, simplifying production and therapeutic use.
Use of D-amino acids in the polypeptide can improve in vivo stability by resisting proteolytic degradation.
Fusion proteins and conjugates can enhance targeting, purification, or prolong half-life, improving therapeutic potentials.
Documented Applications
Therapeutic and prophylactic inhibition of viral infections, especially HIV infection, in hosts including humans.
Use as antiviral agents in compositions for administration via various routes including topical, oral, parenteral, vaginal, rectal, and inhalation.
Administration of nucleic acids or transformed isolated cells, such as genetically modified lactobacilli, to produce antiviral polypeptides in vivo for prevention of sexual transmission of viruses.
Ex vivo virucidal sterilization and viral inhibition in biological samples, such as blood or bodily fluids, or on inanimate objects such as medical equipment and contraceptive devices.
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