1.[Present status and advances in pharmacotherapy for cytomegalovirus retinitis associated with acquired immunodeficiency syndrome].
Wang WW;Ye JJ Zhonghua Yan Ke Za Zhi. 2010 Dec;46(12):1148-52.
Cytomegalovirus retinitis has been the most common opportunistic infection and leading cause of visual loss in AIDS patients. There are five drugs approved by the Food and Drug Administration in the USA for the treatment of cytomegalovirus retinitis: ganciclovir, foscarnet/phosphonoformic acid, valganciclovir, cidofovir and formivirsen. Progress has been made in the treatment of cytomegalovirus retinitis. Nowadays, maribavir, monoclonal antibody MSL-109, cyclopropavir and BAY 38-4766 are entering clinical trials. This review summarizes present status and advances in pharmacotherapy for cytomegalovirus retinitis in AIDS.
2.In vitro activity and mechanism of action of methylenecyclopropane analogs of nucleosides against herpesvirus replication.
Kern ER;Kushner NL;Hartline CB;Williams-Aziz SL;Harden EA;Zhou S;Zemlicka J;Prichard MN Antimicrob Agents Chemother. 2005 Mar;49(3):1039-45.
We have reported previously that methylenecyclopropane analogs of nucleosides have excellent activity against certain members of the herpesvirus family. A second generation, the 2,2-bis-hydroxymethyl derivatives, were synthesized, and 18 compounds were tested for activity in vitro against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), human and murine cytomegalovirus (HCMV and MCMV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Selected analogs were also evaluated against human herpesvirus type 6 (HHV-6) and HHV-8. None of the 18 compounds had activity against HSV-1 or HSV-2, but four were active against VZV by plaque reduction (PR) assay at 50% effective concentration (EC(50)) levels of < or =50 microM. Six of the 18 compounds were active against HCMV by cytopathic effect or PR assays with EC(50)s of 0.5 to 44 microM, and all were active against MCMV by PR (0.3 to 54 microM). Four of the compounds were active against EBV by enzyme-linked immunosorbent assay (<0.3 to 4.4 microM). Four compounds with CMV activity were also active against HHV-6A and HHV-6B (0.7 to 28 microM), and three compounds were active against HHV-8 (5.5 to 16 microM). One of these, ZSM-I-62, had particularly good activity against CMV, HHV-6, and HHV-8, with EC(50)s of 0.
3.Oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models for cytomegalovirus infections.
Kern ER;Bidanset DJ;Hartline CB;Yan Z;Zemlicka J;Quenelle DC Antimicrob Agents Chemother. 2004 Dec;48(12):4745-53.
We reported previously that purine 2-(hydroxymethyl)methylenecyclopropane analogs have good activity against cytomegalovirus infection. A second-generation analog, (Z)-9-[[2,2-bis-(hydroxymethyl)cyclopropylidene]methyl]guanine (ZSM-I-62, cyclopropavir [CPV]), has particularly good activity against murine and human cytomegaloviruses (MCMV and HCMV) in vitro. To determine the oral activity of this compound in vivo, BALB/c or severe combined immunodeficient (SCID) mice infected with MCMV and two models using SCID mice implanted with human fetal tissue and subsequently infected with HCMV were used. In MCMV-infected normal mice, CPV at 10 mg/kg of body weight was highly effective in preventing mortality when administered at 24, 48, or 72 h post-viral inoculation and reduced titers of virus in tissues of SCID mice by 2 to 5 log10. In one HCMV model, human fetal retinal tissue was implanted into the anterior chamber of the mouse eye and inoculated with the Toledo strain of HCMV, and in the second, human fetal thymus and liver tissues were implanted under the kidney capsule of mice and then inoculated with HCMV. In general, replication of HCMV in both types of implant tissue increased from 7 through 21 to 28 days and then gradually decreased to undetectable levels by 8 weeks postinfection.