Potent in vitro Activity of the Albumin Fusion Type 1 Interferons (Albumin-Interferon-Alpha and Albumin-Interferon-Beta) against RNA Viral Agents of Bioterrorism and the Severe Acute Respiratory Syndrome (SARS) VirusSubramanian G.M. · Moore P.A. · Gowen B.B. · Olsen A.L. · Barnard D.L. · Paragas J. · Hogan R.J. · Sidwell R.W.
aHuman Genome Sciences, Inc., Rockville, Md., bInstitute of Antiviral Research, Utah State University, Logan, Utah, cUS Army Medical Research Institute of Infectious Diseases, Fort Detrick, Md., and dUniversity of Georgia, Athens, Ga., USA
Background: The type 1 interferons (INF-α and INF-β) are potent antiviral agents. Albumin-INF-α and albumin-INF-β are novel recombinant proteins consisting of IFN-α or IFN-β genetically fused to human albumin. Methods: The in vitro antiviral activity of albumin-IFN-α was evaluated against representative bioterrorism viral agents and the severe acute respiratory syndrome virus. Antiviral activity was assessed using inhibition of cytopathic effect and neutral red staining. Results: EC50 values for albumin-IFN-α ranged from <0.1 ng/ml for Punta Toro virus to 65 ng/ml for Venezuelan equine encephalitis virus in the neutral red assay. Albumin-IFN-β showed 75- and 360-fold greater in vitro activity than albumin-IFN-α against Ebola virus and severe acute respiratory syndrome, respectively. Conclusion: Further evaluation of these long-acting albumin-IFN fusion proteins as prophylactic or therapeutic agents against these viral agents of bioterrorism in relevant primate models is warranted.
G. Mani Subramanian, MD, PhD
Human Genome Sciences, Inc., 14200 Shady Grove Road
Rockville, MD 20850 (USA)
Tel. +1 301 315 2771, Fax +1 301 279 8799, E-Mail Mani_Subramanian@hgsi.com
G.M.S. and P.A.M. were employed full time by Human Genome Sciences, Inc., at the time of conduct of the project.
Received: April 30, 2007
Accepted after revision: March 3, 2008
Published online: Juni 18, 2008
Number of Print Pages : 5
Number of Figures : 2, Number of Tables : 1, Number of References : 22
Chemotherapy (International Journal of Experimental and Clinical Chemotherapy)
Vol. 54, No. 3, Year 2008 (Cover Date: July 2008)
Journal Editor: Sörgel F. (Nürnberg-Heroldsberg)
ISSN: 0009–3157 (Print), eISSN: 1421–9794 (Online)
For additional information: http://www.karger.com/CHE