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Phosphorothioate Di- And Trinucleotides As A Novel Class Of Anti-Hepatitis B Virus Agents, R. P. Iyer, Y. Jin, A. Roland, John D. Morrey, S. Mounir, B. Korba
Phosphorothioate Di- And Trinucleotides As A Novel Class Of Anti-Hepatitis B Virus Agents, R. P. Iyer, Y. Jin, A. Roland, John D. Morrey, S. Mounir, B. Korba
John D. Morrey
Several nucleoside analogs are under clinical development for use against hepatitis B virus (HBV). Lamivudine (3TC), a nucleoside analog, and adefovir dipivoxil (ADV), an acyclonucleotide analog, are clinically approved. However, long-term treatment can induce viral resistance, and following the cessation of therapy, viral rebound is frequently observed. There continues to be a need for new antiviral agents with novel mechanisms of action. A library of more than 600 di- and trinucleotide compounds synthesized by parallel synthesis using a combinatorial strategy was screened for potential inhibitors of HBV replication using the chronically HBV-producing cell line 2.2.15. Through an iterative process of …
Anti-Hepatitis B Virus Activity Of Ori-9020, A Novel Phosphorothioate Dinucleotide, In A Transgenic Mouse Model, R. P. Iyer, A. Roland, Y. Jin, S. Mounir, B. Korba, Justin G. Julander, John D. Morrey
Anti-Hepatitis B Virus Activity Of Ori-9020, A Novel Phosphorothioate Dinucleotide, In A Transgenic Mouse Model, R. P. Iyer, A. Roland, Y. Jin, S. Mounir, B. Korba, Justin G. Julander, John D. Morrey
John D. Morrey
ORI-9020, a novel dinucleotide, evaluated in transgenic mice expressing hepatitis B virus (HBV), significantly reduced liver HBV DNA (P <= 0.001). Levels of HBeAg and HBsAg in serum and of HBcAg in liver were not affected by treatment. A minimal effective dosage was determined to be between 1.6 and 0.5 mg/kg of body weight/day, which was similar to that observed for adefovir dipivoxil.