The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo

Autoren

S KAPTEIN
T EFFERTH
M LEIS
S RECHTER
S AUEROCHS
M KALMER
C BRUGGEMAN
C VINK
T STAMMINGER
M MARSCHALL

DOI

10.1016/j.antiviral.2005.10.003

ISSN

0166-3542

Ausgabe der Veröffentlichung

2

Zeitschrift

Antiviral Research

Sprache

en

Paginierung

60 - 69

Datum der Veröffentlichung

2006

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.antiviral.2005.10.003

Datum der Datenerfassung

2019

Titel

The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo

Ausgabe der Zeitschrift

69

Data source: Crossref

Abstract

Treatment of human cytomegalovirus (HCMV) infections with any of the currently available antiviral agents is frequently associated with the occurrence of severe complications, seriously threatening the successful outcome of treatment. Therefore, the development of novel antiviral strategies is a challenging goal of current investigations. Previously, we reported that artesunate (ART) is an effective, non-cytotoxic inhibitor of HCMV in vitro. Here, we demonstrate that the efficacy of the antiviral effect of ART is augmented by co-treatment of HCMV-infected fibroblasts with ferrous iron, i.e. Ferrosanol, and/or the iron transfer-mediating molecule holo-transferrin. This could alleviate the HCMV-induced modulation of cell surface expression of adhesion molecule Thy-1, suggesting that ART might be able to prevent pro-inflammatory effects of infection. The iron-enhanced, antiviral effect of ART could also be demonstrated in cultured cells infected with rat cytomegalovirus. Experiments using the RCMV/rat model showed that both the viral DNA load and virus titers in the salivary glands from infected rats were significantly reduced upon treatment with ART. Furthermore, an additive antiviral effect for ART together with each one of conventional anti-HCMV drugs, i.e. ganciclovir, cidofovir or foscarnet, was detected in HCMV-infected fibroblasts. These findings might open new perspectives regarding the use of ART in clinical trials.

Addresses

Department of Medical Microbiology, University Hospital Maastricht, Maastricht, The Netherlands.

Autoren

Suzanne JF Kaptein
Thomas Efferth
Thomas Efferth
Martina Leis
Sabine Rechter
Sabrina Auerochs
Martina Kalmer
Cathrien A Bruggeman
Cornelis Vink
Thomas Stamminger
Manfred Marschall

DOI

10.1016/j.antiviral.2005.10.003

eISSN

1872-9096

Externe Identifier

PubMed Identifier: 16325931

Open access

false

ISSN

0166-3542

Ausgabe der Veröffentlichung

2

Zeitschrift

Antiviral research

Schlüsselwörter

Cells, Cultured
Fibroblasts
Animals
Rats, Inbred Lew
Humans
Rats
Cytomegalovirus
Muromegalovirus
Herpesviridae Infections
Cytomegalovirus Infections
Ferrous Compounds
Sesquiterpenes
Artemisinins
Transferrin
Antimalarials
Antiviral Agents
Drug Therapy, Combination
Specific Pathogen-Free Organisms
Virus Replication
Immunocompromised Host
Male
Artesunate

Sprache

eng

Medium

Print-Electronic

Online publication date

2005

Paginierung

60 - 69

Datum der Veröffentlichung

2006

Status

Published

Datum der Datenerfassung

2005

Titel

The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

69

Data source: Europe PubMed Central

Abstract

Treatment of human cytomegalovirus (HCMV) infections with any of the currently available antiviral agents is frequently associated with the occurrence of severe complications, seriously threatening the successful outcome of treatment. Therefore, the development of novel antiviral strategies is a challenging goal of current investigations. Previously, we reported that artesunate (ART) is an effective, non-cytotoxic inhibitor of HCMV in vitro. Here, we demonstrate that the efficacy of the antiviral effect of ART is augmented by co-treatment of HCMV-infected fibroblasts with ferrous iron, i.e. Ferrosanol, and/or the iron transfer-mediating molecule holo-transferrin. This could alleviate the HCMV-induced modulation of cell surface expression of adhesion molecule Thy-1, suggesting that ART might be able to prevent pro-inflammatory effects of infection. The iron-enhanced, antiviral effect of ART could also be demonstrated in cultured cells infected with rat cytomegalovirus. Experiments using the RCMV/rat model showed that both the viral DNA load and virus titers in the salivary glands from infected rats were significantly reduced upon treatment with ART. Furthermore, an additive antiviral effect for ART together with each one of conventional anti-HCMV drugs, i.e. ganciclovir, cidofovir or foscarnet, was detected in HCMV-infected fibroblasts. These findings might open new perspectives regarding the use of ART in clinical trials.

Date of acceptance

2005

Autoren

Suzanne JF Kaptein
Thomas Efferth
Martina Leis
Sabine Rechter
Sabrina Auerochs
Martina Kalmer
Cathrien A Bruggeman
Cornelis Vink
Thomas Stamminger
Manfred Marschall

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/16325931

DOI

10.1016/j.antiviral.2005.10.003

ISSN

0166-3542

Ausgabe der Veröffentlichung

2

Zeitschrift

Antiviral Res

Schlüsselwörter

Animals
Antimalarials
Antiviral Agents
Artemisinins
Artesunate
Cells, Cultured
Cytomegalovirus
Cytomegalovirus Infections
Drug Therapy, Combination
Ferrous Compounds
Fibroblasts
Herpesviridae Infections
Humans
Immunocompromised Host
Male
Muromegalovirus
Rats
Rats, Inbred Lew
Sesquiterpenes
Specific Pathogen-Free Organisms
Transferrin
Virus Replication

Sprache

eng

Country

Netherlands

Paginierung

60 - 69

PII

S0166-3542(05)00228-7

Datum der Veröffentlichung

2006

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2006

Titel

The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

69

Data source: PubMed

The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo

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