pyrimidinones and Cytomegalovirus-Infections

Human cytomegalovirus terminase complex cleaves the concatemeric genomic viral DNA into unit lengths during genome packaging and particle assembly. Terminase complex ATPase and endonuclease activity is provided by the viral protein pUL89. pUL89 is an attractive drug target because its activities are required for infectious virus production. A domain located in the C-terminus of pUL89 has an RNase H/integrase-like fold and endonuclease activity that can be inhibited by compounds featuring a chelating triad motif. Previously, we developed a novel ELISA approach to screen for pUL89 inhibitors. In this report, we used the ELISA to identify 3-hydroxypyrimidine-2,4-dione as a promising scaffold for pUL89 inhibitor development. Several potent pUL89 inhibitors yielded low micromolar IC

Topics: Cytomegalovirus; Cytomegalovirus Infections; Enzyme Inhibitors; Humans; Metals; Pyrimidinones; Viral Proteins; Virus Replication

We report the case of a patient with non-Hodgkin's lymphoma who, during chemotherapy according to the r-CHOP schedule (rituximab-cyclophosphamide-doxorubicin-vincristine and prednisone), showed a hepatic flare with jaundice. Given the patient's state of asymptomatic carrier of HBsAg, we began a treatment of telbivudine (600 mg/die), resulting in a regression of hepatitis flare and negativization of HBV viraemia.

Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Cyclophosphamide; Cytomegalovirus; Cytomegalovirus Infections; Doxorubicin; Hepatitis B virus; Hepatitis B, Chronic; Humans; Hyperbilirubinemia; Immunocompromised Host; Immunosuppressive Agents; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Nucleosides; Prednisone; Pyrimidinones; Rituximab; Telbivudine; Thymidine; Vincristine; Viremia; Virus Activation

The 2-amino-5-halo-pyrimidinones, which are potent interferon inducers and antiviral agents, were found to be protective against lethal cytomegalovirus (CMV) challenge in weanling or neonatal mice when administered before virus challenge. This protection was dependent upon the dosage of pyrimidinone administered. Weanling mice infected with a sublethal challenge of CMV exhibited moderate to severe immunosuppression as measured by reduced splenic cell blastogenic responses in vitro to the mitogen concanavalin A. Treatment of mice with pyrimidinones during the course of CMV immunosuppression resulted in substantial augmentation of splenic cell blastogenic responses. The degree of augmentation appeared to be dependent on the severity of CMV-induced immunosuppression.

Topics: Animals; Animals, Newborn; Cytomegalovirus Infections; Female; Immune Tolerance; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mitogens; Pyrimidinones; Spleen; Viral Plaque Assay