@article{JTD4688,
author = {Ai-Hong Zeng and Yang-Ying Ou and Ming-Ming Guo and Xuan Dai and De-Zhi Zhou and Rui Chen},
title = {Human embryonic lung fibroblasts treated with artesunate exhibit reduced rates of proliferation and human cytomegalovirus infection in vitro},
journal = {Journal of Thoracic Disease},
volume = {7},
number = {7},
year = {2015},
keywords = {},
abstract = {Background: Cytomegalovirus (CMV) pneumonia is a major cause of death in immunosuppressed patients. Despite the effective treatment with ganciclovir (GCV) and other antiviral agents, the mortality rate remains between 30% to 50%. Recently, the anti-malarial drug artesunate (ART) wasfound to exhibit significant anti-viral activity. Here, we examined the effects of ART on human cytomegalovirus (HCMV) infection and human embryonic lung fibroblast (HELF) proliferation in vitro.
Methods: HELFs infected with the GFP-expressing Towne-BAC strain of HCMV were divided into three treatment groups: Group I, cells treated with ART for 1.5 h before HCMV inoculation; Group II, cells infected with HCMV that was pre-treated with ART for 1.5 h before HCMV inoculation; Group III, cells that were treated with ART at 1.5 h post-HCMV inoculation. GFP expression was observed daily by fluorescence microscopy, and the number of GFP-positive cells in each experimental group was recorded at 4-5 days post-infection. At 10 days post-infection, the viability of cells in each group was recorded. GCV treatment was used as a control.
Results: While no significant effects on cytotoxicity, cell viability, viral infection rates, or antiviral activity were observed upon treatment of Group I or II cells with GCV or low levels of ART, the ART-treated Group III population exhibited significantly reduced rates of infection at drug concentrations higher than 12.5 μM. Similarly, we observed a GCV concentration-dependent reduction in the viral infection rate in Group III cells. Notably, ART-treated, but not GCV-treated, cells also exhibited decreased proliferation. The 50% cytostatic concentrations (CC50) and the half maximal inhibitory concentrations (IC50) of ART and GCV were 54.382 μM and 12.679 μM, and 3.76 M and 14.479 μM, respectively.
Conclusions: In addition to its robust antiviral activity, ART inhibits proliferation of HCMV-infected lung fibroblasts, making it a potential next-generation drug for CMV pneumonia treatment and for reducing fibroproliferation and fibrosis in these patients.},
issn = {2077-6624}, url = {https://jtd.amegroups.org/article/view/4688}
}