In Nebraska, Martin Salia received blood plasma from an Ebola survivor and ZMapp, one of more than a dozen drugs that are being studied for treating Ebola and other filoviruses. No drug has been formally approved. In West Africa, the best treatment currently available includes ensuring that patients have enough fluids, electrolytes and oxygen and that they are treated for secondary infections.
1
4
2
3
Ebola virus
Monoclonal
antibodies
Virus enters host cell
Virus proteins release
viral genome into cell
New virus
“buds” from cell
RNA
Enzymes help
replicate virus
Host cell
C
e
l
l
m
e
m
b
r
a
n
e
1
U.S. Army Medical Research Institute of Infectious Diseases,
2
Phosphorodiamidate morpholino oligomers,
3
Small particle immunopotentiators,
4
University of Washington
*
Developed to target other viruses, such as herpes, influenza, adenovirus and West Nile virus
1
2
3
4
5
INVESTIGATORS Mapp PHAC USAMRIID 1 Tekmira Chimerix Fujifilm Biocryst Inhibikase Sarepta Drexel Unither Novartis Gale Laboratory 4 Defyrus USAMRIID/Zalicus DRUGS ZMapp ZMAb IgG Ebola TKM-Ebola Brincidofovir* Favipiravir* BCX4430 Gleevec PMOs 2 Glucosidase inhibitors Glycosidase inhibitor SMIPs 3 IRF-3 pathway activators IFN alpha Ad5 vector All drugs PATIENTS SPAIN: Miguel Pajares , priest (died) GEORGIA: Nancy Writebol , nurse; Kent Brantly , doctor NEBRASKA: Richard Sacra , doctor TEXAS: Thomas Eric Duncan (died) NEBRASKA: Ashoka Mukpo , journalist FRANCE: A volunteer nurse STRATEGIES Targets the virus before it enters the cell • A cocktail of three monoclonal antibodies, which target the virus (Currently unavailable) • An equal mixture of three antibodies, which attack the virus envelope • Y-shaped antibodies designed to interfere with the Ebola virus Interferes with viral reproduction • Degrades viral RNA, preventing Ebola from replicating • Disrupts enzymes that the virus uses to make copies of itself • Disrupts enzymes that the virus uses to make copies of itself • Disrupts enzymes that the virus uses to make copies of itself • An anti-cancer drug that, in the laboratory, inhibits viral replication • Molecules that bind to viral RNA, blocking gene function • Disrupt the formation of viral proteins in an infected cell Prevents the virus from exiting host cells • Blocks the ability of the virus to leave the host cell Bolsters human cells • Drugs that enhance the human immune response • Stimulate proteins that regulate interferons, which boost the antiviral defenses in host cells • Use of a modified adenovirus to deliver interferon-producing genes to host cells Tests existing drugs approved for other purposes • Screening all FDA-approved drugs for possible activity on filoviruses
Brantly has donated to both Sacra and Mukpo a unit of blood, or convalescent serum, which probably contains antibodies that help check the virus.
SOURCE: Department of Health and Human Services, CDC, NIH, Science Translational Medicine, Viruses, Antiviral Research, Tekmira, Chimerix, Biocryst, staff reports.
