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: 3.94). 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.

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Available from: Igor Resnick, Jul 16, 2014
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    • "As uncovered in the past years, artemisinin-type compounds are also active against cancer cells, human cytomegalovirus (HCMV) infections, and other viral infections, as well as schistosomiasis (Efferth, 2005; Efferth et al., 2008; Liu et al., 2011; Efferth and Krishan, 2016) (Fig. 2b). Randomized double-blind clinical phase II trials on the activity of artemisinin against human cancer and schistosomiasis, as well as preliminary clinical data on HCMV-infected patients, provide striking evidence that the bioactivity of this class of sesquiterpenes goes far beyond malaria treatment (Jansen et al., 2011; Wolf et al., 2011; Pérez del Villar et al., 2012; Krishna et al., 2014). The application of artemisinin for new disease indications has to be further explored in the future. "

    Full-text · Article · Dec 2015 · Phytomedicine
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    • "In addition, ART and chemical ART derivatives exert a very interesting profile of antiviral activities both in vitro and in vivo (Arav-Boger et al., 2010; Auerochs et al., 2011; Cai et al., 2014; Chou et al., 2011; Efferth et al., 2002, 2008; Flobinus et al., 2014; He et al., 2011, 2012, 2013; Kaptein et al., 2006; Milbradt et al., 2009; Reiter et al., 2015a, 2015b; Sharma et al., 2014a, 2014b). To date, a limited number of clinical antiviral treatments (name patient programs, mostly HCMV) have been conducted with ART, in some cases leading to an efficient control of viral infection (Germi et al., 2014; Shapira et al., 2008), but in other cases showing poor benefit or even treatment failure (Lau et al., 2011; Wolf et al., 2011). The mechanism of the anti- HCMV activity has not been explained in detail so far, but initial experimental evidence pointed to the fact that ART and ART-related compounds may act as inhibitors of virus-supportive cellular activation pathways. "
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    ABSTRACT: Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of standard antiviral therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy is based on the exploitation of cell-directed signaling inhibitors. The broad antiinfective drug artesunate (ART) offers additional therapeutic options such as oral bioavailability and low levels of toxic side-effects. Here, novel ART-derived compounds including dimers and trimers were synthesized showing further improvements over the parental drug. Antiviral activity and mechanistic aspects were determined leading to the following statements: (i) ART exerts antiviral activity towards human and animal herpesviruses, (ii) no induction of ART-resistant HCMV mutants occurred in vitro, (iii) chemically modified derivatives of ART showed strongly enhanced anti-HCMV efficacy, (iv) NF-κB reporter constructs, upregulated during HCMV replication, could be partially blocked by ART treatment, (v) ART activity analyzed in stable reporter cell clones indicated an inhibition of stimulated NF-κB but not CREB pathway, (vi) solid-phase immobilized ART was able to bind to NF-κB RelA/p65, and (vii) peptides within NF-κB RelA/p65 represent candidates of ART binding as analyzed by in silico docking and mass spectrometry. These novel findings open new prospects for the future medical use of ART and ART-related drug candidates.
    Full-text · Article · Nov 2015 · Antiviral Research
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    ABSTRACT: Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.
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