Drexel University

Baruch S. Blumberg Institute

Hoffmann-la Roche Inc.

Arbutus Biopharma Corporation

Institute for Hepatitis and Virus Research

Enantigen Therapeutics, Inc.

F. Hoffmann-la Roche Ag

Andrea Cuconati

Timothy Michael Block

Xiaodong Xu

Haitao Guo

Dawei Cai

Tong Xiao

Ju-Tao Guo

Huagang Lu

Changhua Ji

William Alvin Kinney

Yanming Du

Jinhong Chang

John Rogowsky

Described herein are substituted aminothiazoles, compositions comprising same; and methods of making and using same.

Substituted aminothiazoles

The present invention relates to methods and uses for screening anti-hepadnaviral substances, wherein the substances are screened for the capacity to inhibit covalently closed circular (ccc) DNA of a hepadnavirus, like hepatitis B virus. The methods and uses take advantage of cells comprising a nucleic sequence encoding a tagged hepadnavirus e antigen, like Hepatitis B virus e antigen (HBeAg). Furthermore, the present invention provides nucleic acid sequences encoding a tagged hepadnavirus e antigen and proteins encoded thereby. Also kits for use in the screening methods are provided.

Tagged hepadnavirus E antigen and its use in screening antiviral substances

Pharmaceutical compositions of the invention comprise substituted aminothiazoles derivatives having a disease-modifying action in the treatment of diseases associated with unregulated cell growth that include hepatocellular carcinoma, and infection with a hepatitis virus.

Substituted aminothiazoles as inhibitors of cancers, including hepatocellular carcinoma, and as inhibitors of hepatitis virus replication

Tagged hepadnavirus e antigen and its use in screening antiviral substances

Pharmaceutical compositions of the invention comprise covalently closed circular DNA formation inhibitors having a disease-modifying action in the treatment of diseases associated with the formation of covalently closed circular DNA that include hepatitis B infection, and any disease involving formation of covalently closed circular DNA.

Inhibitors of hepatitis B virus covalently closed circular DNA formation and their method of use

Pharmaceutical compositions of the invention comprise triazolopyrimidines useful for the treatment of hepatitis virus in a patient.

Inhibitors of secretion of hepatitis B virus antigens

The present invention describes a unique antiviral screen system. The assay is based on quantitatively monitoring viral activation of host cell beta-interferon (IFN-&#x3b2;) gene expression in a HEK293-derived reporter cell line expressing a firefly luciferase gene under the control of a human IFN-&#x3b2; promoter. Unlike the traditional high throughput antiviral assays that measure either the reduction of viral components/yields or cytopathic effect, the readout of the reporter assay in the present invention is the virus-induced host cellular innate immune response. Hence, the assay allows for identification of compounds that inhibit virus infection. In addition, because induction of IFN is one of the most common attributes of viruses, the assay is applicable to all the viruses that are able to infect the reporter cell line and induce IFN-&#x3b2; expression. Compounds that interfere with viral mediated activation of the interferon pathway in a primary screen, can be further screened with virus-specific assay to confirm their antiviral activity.

Benzodiazepine compounds with anti-flavivirus activity

A pharmaceutical composition comprising an effective amount of a compound of formulas (I-III) and a pharmaceutically acceptable carrier. Methods for treating a hepatitis virus in a patient comprising administering an effective amount of the compound of formulas (I-III) are also presented.

Substituted triazolo[1,5-A]pyrimidines as antiviral agents

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Oreland, PA, United States of America

Andrea Cuconati