Inhibition of Hepatitis B Virus Replication by Drug-Induced Depletion of Nucleocapsids

1. Inhibition of Hepatitis B Virus Replication by Drug-Induced Depletion of Nucleocapsids Presentation By Cristalle Keedy

2. Hepatitis B Virus Basic Facts Hepatitis B is a chronic disease caused by viral infection and it effects the liver tissue and leads to liver cancer and cirrhosis Most prevalent infection in the world Many symptoms that often go unnoticed Contraction similar to HIV Hepadnavirus with partially dsDNA Full negative strand and partial positive strand Linear DNA in circular arrangement due to overlap of +/- strand

3. Replication Cycle

4. Current Hepatitis Vaccine and Treatments Vaccine � subunit vaccine that prevents development and carrier state of disease. It is cost effective and requires two doses. 2. Epivir HBV (3TC) : blocks the production of reverse transcriptase and lowers the concentration of Hep B in the blood 3. Interferon : subcutaneous injections of IF lead to signal transduction in which enhanced gene expression leads to an increase in lymphocytes killing target cells and inhibition of virus replication in infected cells Reverts active infection to a subclinical level

5. Developing Technology Bay 41-4109 and its derivatives (known as HAPs) are drugs that inhibit the formation of viral particles in the core It is enantio-selective and human specific Western blots of cells treated with HAP show reduction of core proteins There is no effect of the drug on transcript levels

6. Mechanism of Inhibition Bay 38-7690 inhibited the transient expression of core protein and synthesis of viral DNA at identical drug concentrations. The amount of HBV core protein is reduced in correlation to the concentration of HAP used. HAP occupies as many binding sites as there are core protein-dimer subunits.

7. HBV Drugs very Specific HAP binding is stereo-specific and reversible (+) is biologically inactive (-) is active form Binding occurs in cells where HBV is replicating Resistance to HAP could be possible, due to findings of amino acid substitution

8. Unstable Core Proteins are Degraded Pulse chase experiment shows that treatment reduces half life of HBV core particle Degradation of core proteins were proteasome mediated

9. CONCLUSIONS HAP inhibits particle formation as an early event After particles formation is inhibited, core proteins fail to stabilize and are degraded Very specific mechanism of action that has valuable potential for HBV therapy Clinical studies needed

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