Ex vivo model of congenital cytomegalovirus infection and new combination therapies

Morere, Lucie; Andouard, D.; Labrousse, François; Saade, Fadi; Calliste, Claude-Alain; Cotin, Sébastien; Aubard, Y.; Rawlinson, William D.; Esclaire, Françoise; Hantz, Sébastien; Ploy, Marie-Cécile; Alain, Sophie

doi:10.1016/j.placenta.2014.11.003

Cited by 28 publications

(22 citation statements)

References 44 publications

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“…The antiviral effect was confirmed against different, multidrug-resistant strains [10,25,27,29] and with different methods, such as the plaque assay and luminescent/fluorescent methods based on the use of transgenic viral strains [24,30,31]. In some cases, the effect of AS was synergistic with antiviral drugs such as maribavir [27,32,33], lamivudine [17], ganciclovir [34], foscarnet, cidofovir, letermovir [33]. However, in vitro data regarding synergism are not always confirmed in other experimental conditions, as for the case reported by Morère, where synergism between maribavir and AS was not confirmed in an ex vivo placenta model [32].…”

Section: Artesunate and Hcmvmentioning

confidence: 97%

“…In some cases, the effect of AS was synergistic with antiviral drugs such as maribavir [27,32,33], lamivudine [17], ganciclovir [34], foscarnet, cidofovir, letermovir [33]. However, in vitro data regarding synergism are not always confirmed in other experimental conditions, as for the case reported by Morère, where synergism between maribavir and AS was not confirmed in an ex vivo placenta model [32]. Moreover, few data obtained with animal models are available.…”

Section: Artesunate and Hcmvmentioning

confidence: 99%

“…Herpesviridae HSV-1 Quinine sulfate in vivo [68,69] EBV Artesunate in vitro [50] Sulfonamides in vitro [182] HCMV Artemisinin in vitro [16] Artesunate in vitro [10,11,16,17,[24][25][26][27][28][29][30][31][32][33][34] Arthemeter in vitro [61,62] HHV-6 Artesunate in vitro [51,53] HHV-6B Artesunate in vitro [52] KSHV Doxycycline in vitro [183] HSE Artemisinin in vivo (mouse) [35] Dihydroartemisinin in vitro [16] KSHV Sulfonamides in vitro [183] RCMV Artesunate in vivo (rat) [11] Polyomaviridae BKPyV Artesunate in vitro [55] JCPyV Artesunate in vitro [54] Mefloquine in vitro [71] Hepadnaviridae HBV Artemisinin, artesunate in vitro [17] Papillomaviridae HPV Artemisinin in vitro [18] Dihydroartemisinin in vivo (dog) [19] Doxycycline in vitro [177]…”

Section: Virus Family Virus Species Drug Type Of Study (Model) Referementioning

confidence: 99%

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The Use of Antimalarial Drugs against Viral Infection

et al. 2020

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In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.

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Section: Artesunate and Hcmvmentioning

confidence: 97%

Section: Artesunate and Hcmvmentioning

confidence: 99%

Section: Virus Family Virus Species Drug Type Of Study (Model) Referementioning

confidence: 99%

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The Use of Antimalarial Drugs against Viral Infection

et al. 2020

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“…The expanding target populations for HCMV antiviral treatment along with the limitations of current anti-HCMV drugs underscore the need for new antiviral agents with different mechanisms of action. The antimalarial artemisinin derivative artesunate was shown to inhibit HCMV in vitro yet has demonstrated limited antiviral efficacy in vivo (11,14,17,(21)(22)(23)(24), prompting our search for more potent anti-HCMV artemisinin derivatives. Here we show that the innovative artemisinin derivative artemisone is a highly potent and noncytotoxic inhibitor of HCMV.…”

Section: Discussionmentioning

confidence: 99%

“…The antimalarial artemisinin derivative artesunate (see Fig. S1 in the supplemental material) has been shown to inhibit CMV replication in vitro and in an experimental animal model, acting via a unique mechanism which involves the inhibition of host cell functions required for virus replication (11)(12)(13)(14)(15)(16)(17)(18). Major examples of such HCMV-supportive cellular functions reported to be inhibited by artesunate in vitro include the HCMV-induced NF-B and Sp1 activation pathways and the virus-modulated cell cycle progression state, both of which are known to support efficient HCMV replication (13,14,19,20).…”

mentioning

confidence: 99%

The Artemisinin Derivative Artemisone Is a Potent Inhibitor of Human Cytomegalovirus Replication

Oiknine‐Djian

Weisblum

Panet

et al. 2018

Antimicrob Agents Chemother

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Human cytomegalovirus (HCMV) is a major cause of disease in immunocompromised individuals and the most common cause of congenital infection and neurosensorial disease. The expanding target populations for HCMV antiviral treatment along with the limitations of the currently available HCMV DNA polymerase inhibitors underscore the need for new antiviral agents with alternative modes of action. The antimalarial artemisinin derivative artesunate was shown to inhibit HCMV yet has demonstrated limited antiviral efficacy, prompting our search for more potent anti-HCMV artemisinin derivatives. Here we show that the innovative artemisinin derivative artemisone, which has been screened for its activity against malaria parasites in human clinical studies, is a potent and noncytotoxic inhibitor of HCMV. Artemisone exhibited an antiviral efficacy comparable to that of ganciclovir (50% effective concentration, 1.20 ± 0.46 μM) in human foreskin fibroblasts, with enhanced relative potency in lung fibroblasts and epithelial cells. Significantly, the antiviral efficacy of artemisone was consistently ≥10-fold superior to that of artesunate in all cells. Artemisone effectively inhibited both laboratory-adapted and low-passage-number clinical strains, as well as drug-resistant HCMV strains. By using quantitative viral kinetics and gene expression studies, we show that artemisone is a reversible inhibitor targeting an earlier phase of the viral replication cycle than ganciclovir. Importantly, artemisone most effectively inhibited HCMV infection in a clinically relevant multicellular model of integral human placental tissues maintained in organ culture. Our promising findings encourage preclinical and clinical studies of artemisone as a new inhibitor against HCMV.

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Prenatal parvovirus B19 infection

Kagan,

Hoopmann,

Geipel

et al. 2024

Arch Gynecol Obstet

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Parvovirus B19 (B19V) causes erythema infectiosum, a.k.a., fifth disease. This disease primarily affects children. It is generally self-limiting and subsides after 1–2 weeks. In pregnancy, the virus can cross the placenta and result in a fetal infection. This may lead to severe fetal anemia, hydrops fetalis, a miscarriage, or intrauterine fetal death. The risk of long-term sequelae also appears to be increased. About one-third of pregnant women are not immune to B19V and, therefore, are at risk to contract a primary infection. The seroconversion rate during pregnancy is generally around 1–2%. During a primary infection, maternal–fetal transplacental transmission of B19V occurs in about 30–50% of the cases and the risk of fetal infection increases with advancing gestational age. The risk of severe fetal anemia or hydrops is around 3–4% overall and is around 6–7% if the primary infection occurs before 20 weeks’ gestation. Fetal monitoring in women with a primary B19V infection includes regular ultrasound examinations looking for evidence of hydrops fetalis and Doppler measurements of the middle cerebral artery peak velocity. Fetal blood sampling is performed if a significant anemia is suspected and, if such is found, an intrauterine blood transfusion is needed. This article provides an overview of the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and management of B19V infection during pregnancy.

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Ex vivo model of congenital cytomegalovirus infection and new combination therapies

Cited by 28 publications

References 44 publications

The Use of Antimalarial Drugs against Viral Infection

The Use of Antimalarial Drugs against Viral Infection

The Artemisinin Derivative Artemisone Is a Potent Inhibitor of Human Cytomegalovirus Replication

Prenatal parvovirus B19 infection

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