Azuvirins: Novel Peptides with Antiviral and Antineoplastic Potential

Non-coding amino acids Significantly smaller than their parent molecule, Azurin Simple structures Easy to manufacture Bind directly to both viral and host proteins to inhibit infection

Antiviral therapeutics HIV HSV Combinatorial therapy with cancer therapeutics Radio-sensitizers adjuvant Small-molecule adjuvant

Researchers at UCLA have developed and reliably purified a new family of peptides, termed "Azuvirins," that demonstrate anti-neoplastic and anti-viral properties. Many of the peptides effectively bind a group of surface proteins involved in human cancer progression. The researchers demonstrated that low concentrations of Azuvirins, combined with a known radio-sensitizer compound, could improve cancer cell sensitivity to radiation over 10-fold. This result was corroborated in an animal model of lung cancer, where radiation therapy was significantly more effective in reducing tumor volume in the presence of Azuvirins. In addition, multiple Azuvirins have demonstrated efficacy in binding to surface proteins involved in HIV-1 and herpes simplex virus infection. The Azuvirins could completely block viral entry in vitro at therapeutically relevant concentrations, suggesting that they could serve as potent anti-viral therapeutics.

Patent Number: US20130029903A1
Application Number: US13342710A
Inventor: Ruchala, Piotr P. | Lehrer, Robert I.
Priority Date: 3 Jan 2011
Priority Number: US20130029903A1
Application Date: 3 Jan 2012
Publication Date: 31 Jan 2013
IPC Current: C07K000708 | A61K003808 | A61K003810 | A61K003816 | A61M003700 | A61P003114 | A61P003500 | C07K000706 | C07K001400 | C12N000509 | C12N001300
US Class: 5140037 | 4351731 | 435375 | 5140193 | 5140213 | 5140214 | 5140215 | 5140216 | 530324 | 530325 | 530326 | 530327 | 530328 | 600001 | 604020
Title: Azuvirin Peptides
Usefulness: Azuvirin Peptides
Summary: The peptide is useful for: delivering a therapeutic agent to a cancer cell, the cancer cell is a carcinoma including a small cell lung carcinoma; and treating or preventing a viral infection including a retroviral infection (all claimed), preferably HIV-1, HIV-2, feline immunodeficiency virus, human T lymphotropic virus, and simian immunodeficiency virus infection. The peptide is useful for preventing tumors of colon, duodenal, prostate, breast, melanoma, ductal, hepatic, pancreatic, renal, endometrial, stomach, dysplastic oral mucosa, polyposis, invasive oral cancer, transitional and squamous cell urinary carcinoma, neurological malignancies such as neuroblastoma and gliomas, and hematological malignancies such as childhood acute leukemia, non-Hodgkin's lymphomas, chronic lymphocytic leukemia, malignant cutaneous T-cells, mycosis fungoides, non-mycosis fungoides cutaneous T-cell lymphoma, lymphomatoid papulosis, T-cell rich cutaneous lymphoid hyperplasia, bullous pemphigoid, discoid lupus erythematosus and lichen planus. The ability of the azuvirin peptide to bind ephrin receptor (rhEphA2) was tested in mouse using in vivo model. The result showed that AzV36-Nic peptide exhibited dissociation constant value of 425± 226.
Novelty: New isolated azuvirin peptide, useful for delivering therapeutic agent to cancer cell including small cell lung carcinoma, and treating or preventing a viral infection such as e.g. HIV-1, HIV-2 and feline immunodeficiency virus infection

Disease Diagnostic/Treatment

HIV

8716246

State Of Development

The Azuvirin peptides are being tested in laboratory models of viral infection and transmission. The researchers also intend on testing their radio-sensitizing ability in other cancer models and determining their toxicity profile.

Background

Targeted radiation therapy has been a mainstay of treatment for human cancers for decades. The development of compounds that sensitize malignancies to radiation has significantly enhanced its efficacy. The ability of "radio-sensitizer" compounds to improve therapy is dependent on their entry into cancerous cells. However, the toxic effects of most radio-sensitizing compounds on the body limit their administration to patients. Therefore, there is a great need to develop novel compounds or delivery systems that boost the uptake of radio-sensitizing compounds into tumors. Improved uptake of radio-sensitizing compounds into tumors could drastically improve the response to therapy and reduce the duration of treatment.

Persistent viral infections have enormous global health and economic impacts. There are nearly 5 million new HIV infections every year and more than 1 in 6 Americans is infected with HSV. The highly adaptive nature of these viruses allows drug resistance to develop against targeted therapy. These drug-resistant properties necessitate therapies that target multiple, independent mechanisms involved in viral infection, replication, and transmission. There is an obvious need to develop novel drugs that inhibit viral infection and reduce the amount of virus in a patient. Reducing viral propagation through targeted-inhibition of multiple mechanisms would have an enormous impact in reducing the viral infectivity and transmission of patients.

Additional Technologies by these Inventors

• Retrocyclins: Antiviral Circular Minidefensins that Protect Against Human Immunodeficiency Virus and Herpes Simplex Viruses

Tech ID/UC Case

22312/2010-079-0

Related Cases

2010-079-0

USA

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