Twin base linkers for virus inactivation
Inventors
Webster, Thomas J. • Johanson, Mark A.
Assignees
Northeastern University Boston • Audax Medical Inc
Publication Number
US-12090209-B2
Publication Date
2024-09-17
Expiration Date
2041-04-15
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Abstract
Functionalized twin base linkers (TBLs) bind to and deactivate viruses by preventing their entry into cells. Functionalization of TBLs allows them to specifically bind to surface proteins of viruses, where they form structures that limit virus entry into cells and prevent viruses from replicating.
Core Innovation
The invention provides functionalized twin base linkers (TBLs) designed to bind to and deactivate viruses by preventing their entry into cells. The TBLs consist of two linked nucleic acid bases with guanine- and cytosine-like hydrogen bond pairing capability, forming supramolecular structures such as hollow nanotubules. Functionalization through the addition of peptides, antibodies, aptamers, or other targeting moieties allows TBLs to specifically bind to viral surface proteins.
Once bound, these functionalized TBLs form structures on the viral surface that limit the virus's ability to attach to and enter target cells, thereby preventing replication. This approach leverages the multivalent binding and self-assembly capability of the TBLs, enhancing affinity through cooperative interactions between multiple targeting moieties and the viral proteins.
The problem being solved is the need for materials that can effectively and specifically inhibit viral entry and replication in mammalian cells. Conventional uses of TBLs included drug delivery, but there remains a lack of targeted nanomaterials that deactivate viruses such as SARS-CoV-2 or influenza by direct binding to viral surface proteins, thus addressing the global need for antiviral therapeutics that function through physical blockage of infection pathways.
Claims Coverage
There are two independent claims, each representing a key inventive feature in this patent.
Antiviral compositions comprising functionalized twin base linker (TBL) molecules
- An antiviral composition that includes a plurality of functionalized twin base linker (TBL) molecules with a structure formed by twin nucleic acid bases linked by a chain of 4 to about 20 atoms containing carbon, nitrogen, and/or oxygen. - The TBLs are further characterized by a peptide moiety containing from about 2 to about 20 L- and/or D-amino acids. - Optionally, one or more targeting moieties, capable of specifically binding a surface-accessible protein of a virus to deactivate the virus, are covalently linked to the peptide moiety, or the peptide moiety itself is capable of this specific binding if targeting moieties are absent.
Method of treating or preventing viral infection by administering the antiviral composition
- A method for aiding in treating or preventing a viral infection by administering the functionalized TBL antiviral composition to a subject in need thereof. - The method encompasses the composition’s use against a broad range of viruses including, but not limited to, coronaviruses, SARS-CoV-2, influenza A and B, ebola, HIV, adenovirus, rhinovirus, hepatitis B and C, MERS, measles, mumps, and chickenpox viruses. - Therapeutic effect is provided by reduction or prevention of cellular entry, replication, and/or symptoms of viral infection in the subject.
The inventive features are centered on the creation of targeted, functionalized twin base linker molecules for antiviral compositions, and a method of preventing or treating viral infections in subjects by administering such compositions, with specific molecular designs enabling highly selective viral surface binding and deactivation.
Stated Advantages
Functionalized TBLs specifically bind to viral surface proteins, effectively preventing viral entry into cells and subsequent replication.
The TBL compositions provide a versatile antiviral approach applicable to a wide range of viruses infecting mammalian cells, including emerging viral variants.
The antiviral compositions inhibit death of mammalian cells caused by viral infection, offering protection to host cells.
Targeted binding affinity is enhanced due to multivalent interactions via multiple targeting moieties on the TBLs.
Documented Applications
Treatment or prevention of viral infections in humans or other mammals, including but not limited to infections caused by coronavirus, SARS-CoV-2, influenza A and B, ebola virus, HIV, adenovirus, rhinovirus, hepatitis B, hepatitis C, MERS virus, measles virus, mumps virus, and chickenpox virus.
Use in protecting mammalian cells, such as human dermal fibroblasts, from death caused by viruses including rhinovirus, influenza A, and influenza B, as demonstrated in in vitro studies.
Administration as an injectable liquid or aerosol formulation for direct introduction into the body or lungs, where monomers may self-assemble into nanostructures with antiviral activity.
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