Evidence for clinical activity of artesunate in multidrug-resistant herpes simplex infection following HSCT

Sellar, Rob S.; Ward, Katherine N.; Thomson, Kirsty; Peggs, Karl S.

doi:10.1038/bmt.2012.46

Cited by 15 publications

(6 citation statements)

References 11 publications

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“…Apart from compounds acting on pathways involved in the recognition of HSV, other immunomodulatory strategies aimed at reducing the inflammatory response during HSE were also evaluated in animal models. Artesunate and the mTOR inhibitor rapamycin are immunomodulatory drugs occasionally used for the treatment of infections caused by multidrug-resistant herpesviruses (cytomegalovirus and HSV) in immunocompromised patients (208,209). Our group evaluated the efficacy of combining valacyclovir with artesunate and rapamycin to improve the outcome of HSE in mice (210).…”

Section: Other Experimental Immunomodulatory Strategiesmentioning

confidence: 99%

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Piret

Boivin

2020

Clin Microbiol Rev

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SUMMARY Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation.

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Section: Other Experimental Immunomodulatory Strategiesmentioning

confidence: 99%

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Piret

Boivin

2020

Clin Microbiol Rev

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“…In 2008, a patient with recurrent multiresistant CMV infection was successfully treated with artesunate (19), and since then 7 more transplant patients with CMV infections were treated with varying success (20,21). Recently, a patient with multidrug-resistant herpes simplex virus 2 (HSV-2) infection (22) and a child with human herpesvirus 6B (HHV-6B) myocarditis (23) were successfully treated with artesunate. In addition, antiviral activity in vitro has also been found against other herpesviruses, including herpes simplex virus 1 (17), Epstein-Barr virus (24), and human herpesvirus 6A (25), and also to some extent against nonherpesviruses, such as hepatitis B virus (26), hepatitis C virus (27), HIV-1 (17), and bovine viral diarrhea virus (28).…”

mentioning

confidence: 99%

Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells

Sharma

Marschall

Henriksen

et al. 2014

Antimicrob Agents Chemother

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dPolyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 M. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentrationdependent manner. Artesunate at 10 M reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 M reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2=-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G 0 or G 2 phase. Both the antiproliferative and antiviral effects of artesunate at 10 M were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions.

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“…However, clinical case reports have shown an encouraging outlook for this medication. Thus, Sellar et al reported the effectiveness of using artesunate for treating reactivated intractable HSV1/2 strain, which is multiresistant to acyclic nucleoside analogs, in patients who underwent allogeneic bone marrow transplantation 17 . Kumaran et al reported a child's recovery from myocarditis due to chromosomally integrated HHV‐6A, which is usually resistant to the action of acyclic guanosine analogs 18 .…”

Section: Discussionmentioning

confidence: 99%

“…16 It is necessary to compare the effectiveness of artesunate with a complex alternative mechanism of virostatic effect with traditional drugs valaciclovir and valganciclovir based on acyclic guanosine analogs with limited clinical efficacy. It has been shown that artesunate can be effective in managing herpes virus infections caused by multidrug-resistant strains 17 and chromosomally integrated forms 18 where valacyclovir and valganciclovir are usually ineffective. Comparative studies could provide insight into how to optimize treatment strategies in patients with ME/CFS.…”

Section: Introductionmentioning

confidence: 99%

A comparative study of valaciclovir, valganciclovir, and artesunate efficacy in reactivated HHV‐6 and HHV‐7 infections associated with chronic fatigue syndrome/myalgic encephalomyelitis

Maltsev

2022

Microbiology and Immunology

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This study aimed to compare the efficacy of valaciclovir, valganciclovir, and artesunate in treating chronic reactivated human herpesvirus type 6 (HHV-6) and human herpesvirus type 7 (HHV-7) infection associated with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). From 255 patients (192 cases) with reactivated HHV-6 and HHV-7 infections (confirmed based on blood leukocyte PCR), valaciclovir, valganciclovir, or artesunate was administered at a dose of 3000, 900, and 100 mg/day, respectively, for 3 months (study group). The control group consisted of similar patients with ME/CFS (n = 63) not taking any antiviral drugs. The significance of differences was evaluated by Student's t-test and the nonparametric criterion-the number of Z-signs. Negative PCR results in patients with HHV-6 and HHV-7 treated with valaciclovir was achieved in 26% and 23% (first month), 34%, and 28% (second month), 37% and 34% of cases (third month), respectively (P < 0.05; Z < Z 0.05 ). The same results with valganciclovir were obtained in 35% and 33% (first month), 44% and 39% (second month), 48% and 45% of cases (third month), but with artesunate in 44% and 41% (first month), 57% and 53% (second month), 68% and 63% of cases (third month), respectively (P < 0.05; Z < Z 0.05 ). Artesunate is more effective than valganciclovir and valacyclovir in patients with ME/CFS with reactivated HHV-6 and HHV-7 infections.

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Evidence for clinical activity of artesunate in multidrug-resistant herpes simplex infection following HSCT

Cited by 15 publications

References 11 publications

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells

A comparative study of valaciclovir, valganciclovir, and artesunate efficacy in reactivated HHV‐6 and HHV‐7 infections associated with chronic fatigue syndrome/myalgic encephalomyelitis

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