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) virus.
BACKGROUND
The type 1 interferons (INF-alpha and INF-beta) are potent antiviral agents. Albumin-INF-alpha and albumin-INF-beta are novel recombinant proteins consisting of IFN-alpha or IFN-beta genetically fused to human albumin.


METHODS
The in vitro antiviral activity of albumin-IFN-alpha 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
EC(50) values for albumin-IFN-alpha 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-beta showed 75- and 360-fold greater in vitro activity than albumin-IFN-alpha against Ebola virus and severe acute respiratory syndrome, respectively.


CONCLUSIONS
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.
Human Genome Sciences, Inc., Rockville, MD 20850, USA. Mani_Subramanian@hgsi.com
G Mani
GM
Subramanian
Paul A
PA
Moore
Brian B
BB
Gowen
Aaron L
AL
Olsen
Dale L
DL
Barnard
Jason
J
Paragas
Robert J
RJ
Hogan
Robert W
RW
Sidwell
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D023482:Bioterrorism; D002460:Cell Line; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000187:drug effects / Q000502:physiology; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C517868:albumin interferon; D016899:Interferon-beta