Anti-viral cnidarins
Inventors
O'Keefe, Barry R. • McMahon, James B. • Ramessar, Koreen • Xiong, Chang-yun
Assignees
US Department of Health and Human Services
Publication Number
US-11034736-B2
Publication Date
2021-06-15
Expiration Date
2035-01-09
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Abstract
An isolated and purified nucleic acid molecule that encodes a polypeptide comprising at least eight contiguous amino acids of SEQ ID NO: 1, 2, or 3, wherein the at least eight contiguous amino acids have anti-viral activity, as well as an isolated and purified nucleic acid molecule that encodes a polypeptide comprising at least eight contiguous amino acids of SEQ ID NO: 1, 2, or 3, wherein the at least eight contiguous amino acids have anti-viral activity, a vector comprising such an isolated and purified nucleic acid molecule, a host cell comprising the nucleic acid molecule, optionally in the form of a vector, a method of producing an antiviral polypeptide or conjugate thereof, the anti-viral polypeptide itself, a conjugate or fusion protein comprising the anti-viral polypeptide, and compositions comprising an effective amount of the anti-viral polypeptide or conjugate or fusion protein thereof. Further provided are methods of inhibiting prophylactically or therapeutically a viral infection of a host.
Core Innovation
The invention provides isolated and purified anti-viral polypeptides called cnidarins, comprising at least eight contiguous amino acids of SEQ ID NO: 1, 2, or 3, with anti-viral activity. These polypeptides are optionally part of fusion proteins or conjugates, and methods include producing these polypeptides via expression of nucleic acid molecules encoding them. The invention also covers vectors comprising such nucleic acid molecules, host cells containing these vectors, and compositions comprising effective amounts of the anti-viral polypeptides or their conjugates. The polypeptides specifically inhibit viral infections such as HIV, including HIV-1 and HIV-2.
The problem being addressed is the global health issue of HIV/AIDS, which remains a significant challenge due to factors such as emergence of resistant viruses, cross-resistance to drugs, and long-term toxicity of current antiretroviral treatments. The epidemic particularly affects women in sub-Saharan Africa, demanding development of safe, effective, and female-controlled prevention methods like microbicides. Existing microbicides often have limited efficacy or safety concerns, underscoring the need for novel non-antiretroviral anti-HIV agents with potent antiviral activity.
Claims Coverage
The claims include six inventive features focused on conjugates, compositions, production methods, and therapeutic methods involving anti-viral polypeptides comprising SEQ ID NO: 1 or 3 or their C-terminal truncations.
Anti-viral conjugate comprising polypeptide and additional component
A conjugate comprising an anti-viral polypeptide comprising SEQ ID NO: 1 or 3, or SEQ ID NO: 1 or 3 with a C-terminal truncation of 1-60 amino acids, and at least one additional component selected from polyethylene glycol, albumin, dextran, a toxin, an immunological reagent, a virus, a viral envelope glycoprotein, an antiviral agent, or a solid support matrix.
Anti-viral polypeptide with C-terminal truncation
An anti-viral polypeptide comprising SEQ ID NO: 1 or 3 with a C-terminal truncation of 1-60 amino acids.
Composition comprising conjugate and carrier
A composition comprising a pharmaceutically acceptable carrier and the aforementioned conjugate comprising an anti-viral polypeptide.
Method of producing an anti-viral polypeptide
A method of producing an anti-viral polypeptide comprising SEQ ID NO: 1 or 3 or with a C-terminal truncation of 1-60 amino acids by obtaining a cnidarin from Synthecium, sequencing it, synthesizing corresponding DNA, subcloning into expression vector, delivering the vector into polypeptide-producing cells, and allowing expression.
Method of inhibiting HIV-1 replication by administering anti-viral polypeptide
A method of inhibiting HIV-1 replication in a host by administering a composition comprising an anti-viral polypeptide comprising SEQ ID NO: 1 or 3 or with a C-terminal truncation of 1-60 amino acids, thereby inhibiting viral replication.
Method of inhibiting HIV-1 replication with additional composition components
The method of inhibiting HIV-1 replication wherein the composition further comprises at least one additional component selected from polyethylene glycol, albumin, dextran, a toxin, an immunological reagent, a virus, a viral envelope glycoprotein, an antiviral agent, or a solid support matrix.
The claims cover anti-viral conjugates and compositions comprising polypeptides of SEQ ID NO: 1 or 3 or their C-terminal truncations, methods for producing these polypeptides via recombinant expression in host cells, and methods of therapeutically inhibiting HIV-1 replication through administration of these polypeptides and compositions with optional additional components.
Stated Advantages
Potent anti-HIV activity of cnidarin proteins at picomolar to low-nanomolar concentrations.
Distinct viral fusion inhibition mechanism without affecting viral attachment, suggesting a novel mode of antiviral action.
Specific binding to HIV gp120 envelope glycoprotein with no glycosylation required for binding activity.
Potential for use in combination therapies with other microbicidal agents.
Capability of cnidarin to be produced recombinantly, allowing large-scale production and engineering of variants.
Documented Applications
Prophylactic and therapeutic inhibition of viral infections, specifically HIV (e.g., HIV-1 and HIV-2) in hosts.
Use in microbicidal compositions to prevent sexual transmission of HIV via topical vaginal, rectal, oral, or penile administration.
Ex vivo use for removing or inactivating infectious virus from biological samples such as blood, blood products, sperm, tissues, and organs.
Use in compositions applied to contraceptive devices (e.g., condoms, diaphragms, cervical caps, vaginal rings, sponges) for prevention of viral transmission.
Delivery using genetically engineered host cells, including probiotic bacteria, expressing cnidarin for continuous antiviral effect in vivo.
Inducing immune responses against viruses through administration of compositions comprising non-infectious naturally occurring virus and cnidarin-containing compositions.
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