title: Human embryonic lung fibroblasts treated with artesunate exhibit reduced rates of proliferation and human cytomegalovirus infection in vitro.
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.
authors.affiliation: 1 Department of Emergency, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China ; 2 Department of Pediatrics, 3 Department of Respiratory Diseases, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Ai-Hong
authors.initials: AH
authors.lastname: Zeng
authors.affiliation: 1 Department of Emergency, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China ; 2 Department of Pediatrics, 3 Department of Respiratory Diseases, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Yang-Ying
authors.initials: YY
authors.lastname: Ou
authors.affiliation: 1 Department of Emergency, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China ; 2 Department of Pediatrics, 3 Department of Respiratory Diseases, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Guo
authors.affiliation: 1 Department of Emergency, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China ; 2 Department of Pediatrics, 3 Department of Respiratory Diseases, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Dai
authors.affiliation: 1 Department of Emergency, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China ; 2 Department of Pediatrics, 3 Department of Respiratory Diseases, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: De-Zhi
authors.initials: DZ
authors.lastname: Zhou
authors.affiliation: 1 Department of Emergency, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China ; 2 Department of Pediatrics, 3 Department of Respiratory Diseases, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
keywords: Human cytomegalovirus (HCMV); artesunate (ART); lung fibroblast; pneumonia