Article

Human cytomegalovirus kinetics following institution of artesunate after hematopoietic stem cell transplantation.

Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Antiviral research (Impact Factor: 3.61). 03/2011; 90(3):183-6. DOI: 10.1016/j.antiviral.2011.03.184
Source: PubMed

ABSTRACT The anti-malaria drug artesunate has been shown to be an effective inhibitor of cytomegalovirus (CMV) in vitro, in an experimental animal model, and in a recent single-case clinical use. In this first case-series of 6 stem cell transplant recipients who received preemptive artesunate treatment for CMV infection, we have examined the viral kinetics following institution of artesunate, and employed first-phase viral kinetics studies to calculate its antiviral effectiveness. Two patients demonstrated a rapid 0.8-2.1 log viral load decline by 7 days, with a viral decay half-live of 0.9-1.9 days. Four patients demonstrated a continued yet stalled viral growth slope during treatment. No adverse events were noted in treatment courses of up to 28 days. Overall, a divergent antiviral efficacy was revealed, ranging from 43% to 90%, which appeared to be primarily dependent on the virus baseline growth dynamics. Further dose escalation studies are needed to examine the role of artesunate in the treatment of CMV infection in the transplantation setting.

0 Bookmarks
 · 
194 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The review highlights recent advances in our understanding and therapy of CMV infection•A number of new antiviral drugs are currently in late stage development, and these are discussed•These drugs are orally administered and may provide effective prophylaxis if toxicities are not limiting•Routine application of virus-specific adoptive T cell therapies has also moved closer to becoming a reality, with late stage clinical studies recently completed•The role of other cell types, in particular NK cells, in controlling viral infection continues to be evaluated in both pre-clinical and clinical settings
    Biology of Blood and Marrow Transplantation 11/2014; 21(2S). DOI:10.1016/j.bbmt.2014.11.002 · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The human JC polyomavirus (JCPyV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). A growing number of patients with induced or acquired immunosupression are at risk and no effective antiviral therapy is presently available. The widely used antimalarial drug artesunate has shown broad antiviral activity in vitro but, as yet, limited clinical success. The aim of this study was to investigate the effect of artesunate on JCPyV replication in vitro. The permissivity for JCPyV MAD-4 was first compared in four cell lines, and the monkey kidney cell line COS-7 was selected. Artesunate caused a concentration-dependent decrease in extracellular JCPyV DNA load 96 hours postinfection with an EC50 of 2.9 μM. This effect correlated with a decreased expression of capsid protein VP1, and a reduced release of infectious viral progeny. For concentrations below 20 μM, a transient reduction in cellular DNA replication and proliferation was seen, while for higher concentrations, some cytotoxicity was detected. A selective index of 16.6 was found when cytotoxicity was calculated based on cellular DNA replication in mock-infected cells but interestingly cellular DNA replication in JCPyV-infected cells was stronger affected. In conclusion, artesunate is efficacious in inhibiting JCPyV replication at micromolar concentrations which are achievable in plasma. The inhibition at EC50 probably reflects an effect on cellular proteins and involves transient cytostatic effects. Our results together with the favorable distribution of the active metabolite dihydroartemisinin to the central nervous system, suggests a potential use in patients with PML.
    Antimicrobial Agents and Chemotherapy 08/2014; 58(11). DOI:10.1128/AAC.03714-14 · 4.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human herpesvirus 6 (HHV-6) infections are typically mild and in rare cases can result in encephalitis. A common theme among all the herpesviruses, however, is the reactivation upon immune suppression. HHV-6 commonly reactivates in transplant recipients. No therapies are approved currently for the treatment of these infections, although small studies and individual case reports have reported intermittent success with drugs such as cidofovir, ganciclovir, and foscarnet. In addition to the current experimental therapies, many other compounds have been reported to inhibit HHV-6 in cell culture with varying degrees of efficacy. Recent advances in the development of new small molecule inhibitors of HHV-6 will be reviewed with regard to their efficacy and spectrum of antiviral activity. The potential for new therapies for HHV-6 infections will also be discussed, and they will likely arise from efforts to develop broad spectrum antiviral therapies for DNA viruses.
    Current Opinion in Virology 10/2014; 9:148–153. DOI:10.1016/j.coviro.2014.09.019 · 6.30 Impact Factor

Full-text (2 Sources)

Download
15 Downloads
Available from
Jul 16, 2014