Therapeutic potential of the heme oxygenase-1 inducer hemin against Ebola virus infection.
Hanxia Huang, Krishnamurthy Konduru, Veronica Solovena, Zhao-Hua Zhou, Namita Kumari, Kazuyo Takeda, Sergei Nekhai, Sina Bavari, Gerardo G Kaplan, Kenneth M Yamada, Subhash Dhawan
Author Information
Hanxia Huang: Food and Drug Administration, Silver Spring, Maryland.
Krishnamurthy Konduru: Food and Drug Administration, Silver Spring, Maryland.
Veronica Solovena: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland.
Zhao-Hua Zhou: Food and Drug Administration, Silver Spring, Maryland.
Namita Kumari: Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington DC.
Kazuyo Takeda: Food and Drug Administration, Silver Spring, Maryland.
Sergei Nekhai: Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington DC.
Sina Bavari: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland.
Gerardo G Kaplan: Food and Drug Administration, Silver Spring, Maryland.
Kenneth M Yamada: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
Subhash Dhawan: Food and Drug Administration, Silver Spring, Maryland.
Promising drugs to treat Ebola virus (EBOV) infection are currently being developed, but so far none has shown efficacy in clinical trials. Drugs that can stimulate host innate defense responses may retard the progression of EBOV disease. We report here the dramatic effect of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of EBOV replication. Treatment of primary monocyte-derived macrophages (MDM), Vero E6 cells, HeLa cells, and human foreskin fibroblasts (HFF1) with hemin reduced EBOV infection by >90%, and showed minimal toxicity to infected cells. Inhibition of HO-1 enzymatic activity and silencing HO-1 expression prevented the hemin-mediated suppression of EBOV infection, suggesting an important role for induction of this intracellular mediator in restricting EBOV replication. The inverse correlation between hemin-induced HO-1 and EBOV replication provides a potentially useful therapeutic modality based on the stimulation of an innate cellular response against Ebola infection.
