Anti-viral griffithsin compounds, compositions and methods of use
Inventors
O'Keefe, Barry • Mori, Toshiyuki • McMahon, James B.
Assignees
US Department of Health and Human Services
Publication Number
US-8088729-B2
Publication Date
2012-01-03
Expiration Date
2026-12-01
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Abstract
A method of inhibiting a viral infection of a host comprising administering to the host an anti-viral griffithsin polypeptide comprising SEQ ID NO: 3 or a fragment thereof comprising at least eight contiguous amino acids, a nucleic acid encoding the anti-viral polypeptide, or an antibody to the anti-viral polypeptide. A method of inhibiting a virus in a sample comprising contacting the sample with an anti-viral griffithsin polypeptide or antibody thereto also is provided.
Core Innovation
The invention provides anti-viral griffithsin polypeptides, including the polypeptide comprising SEQ ID NO: 3 or functional fragments thereof comprising at least eight contiguous amino acids, nucleic acids encoding such polypeptides, antibodies to these polypeptides, and compositions comprising these agents. The invention further provides methods of inhibiting viral infection in a host by administering the anti-viral griffithsin polypeptide or its antibody, including prophylactic and therapeutic approaches. Methods also include contacting samples with griffithsin or antibodies to remove or inhibit viruses. The invention encompasses recombinant production methods, conjugates, fusion proteins, and purified compositions of griffithsin and its related molecules.
The problem being addressed relates to the continued global threat posed by viruses such as retroviruses including HIV, influenza viruses including H5N1, hepatitis C virus, severe acute respiratory syndrome (SARS) virus, and Ebola virus. Existing therapeutic agents and vaccines have limitations including toxicity, insufficient therapeutic indices, rapid viral mutation leading to resistance, or lack of efficacy. There is a critical need for new antiviral agents that act early in the viral replicative cycle, neutralize virus by specific binding, inhibit spread and infection of new cells, have broad activity against diverse viral strains, resist degradation, and are economical to produce. Specifically, the invention addresses the need for novel methods and compositions for preventing and treating viral infections, including topical microbicides for preventing HIV transmission and agents active against pandemic influenza strains.
Claims Coverage
The patent contains one independent claim that focuses on a method of inhibiting certain viral infections using an anti-viral polypeptide.
Method of inhibiting a viral infection by administering an anti-viral polypeptide
A method of inhibiting a viral infection in a host by administering to the host an anti-viral polypeptide comprising SEQ ID NO: 3. The viral infections treated include Hepatitis C viral infection, Severe Acute Respiratory Syndrome (SARS) viral infection, H5N1 viral infection, or Ebola viral infection, resulting in inhibition of the viral infection.
Topical administration of the anti-viral polypeptide
The anti-viral polypeptide is administered topically to the host, specifically to the respiratory system, enhancing localized inhibition of viral infections.
Administration as an inhalant formulation
The anti-viral polypeptide can be administered as an inhalant formulated as an aerosol or microparticulate powder for targeted delivery to respiratory sites.
Use of non-glycosylated anti-viral polypeptides
The anti-viral polypeptide used is non-glycosylated, which can be advantageous for recombinant production and antiviral activity.
Inclusion of specific polypeptide sequences and conjugates
The anti-viral polypeptide comprises the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 5. It can be administered as part of a polypeptide conjugate incorporating additional functional moieties.
The independent claim covers methods of administering the anti-viral griffithsin polypeptide comprising SEQ ID NO: 3 to inhibit infections by specified viruses, with inventive features relating to formulation, mode of administration, glycosylation state, sequence variants, and conjugates enhancing antiviral efficacy and delivery.
Stated Advantages
The anti-viral polypeptide acts as a virucide by binding to high mannose oligosaccharide constituents of viral envelope glycoproteins, thereby inhibiting viral binding, fusion, and entry.
It has broad-spectrum antiviral activity against diverse strains and isolates of viruses including retroviruses like HIV, influenza (including H5N1), SARS, hepatitis C, and Ebola viruses.
The compositions can be administered prophylactically or therapeutically in various forms such as topical application, inhalants, or systemic administration.
Recombinant production methods allow economical and stable production of griffithsin and derivatives, including conjugates and fusion proteins.
The polypeptides and their conjugates retain antiviral activity, are resistant to degradation, and are useful in combination therapies to prevent transmission or treat infection by resistant viral strains.
Documented Applications
Therapeutic and prophylactic inhibition of viral infections including HIV-1, HIV-2, SIV, influenza virus (notably H5N1), hepatitis C virus, SARS virus, and Ebola virus in human and animal hosts.
Topical microbicides for prevention of HIV sexual transmission, including vaginal, rectal, oral, and penile administration methods.
Removal or inactivation of virus from biological samples such as blood, blood products, sperm, cells, tissues, and organs, including applications in transfusions, transplantation, and dialysis.
Use in formulations attached to solid support matrices, such as contraceptive devices (condoms, diaphragms, cervical caps, vaginal rings, sponges) for prophylactic use against viral infections.
Use as antiviral agents in compositions combined with other antiviral drugs for synergistic or complementary therapy.
Induction of immune responses by administering naturally-occurring, non-infectious virus rendered non-infectious by griffithsin or via anti-idiotypic antibodies for vaccine development.
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