Combining two cancer drugs improves survival of mice infected with dengue or Ebola viruses


Dengue virus is a member of the virus genus Flavivirus. Ebola virus is one of five known viruses within the genus Ebolavirus. The two viruses have very little in common. But now scientists find that a combination of two approved cancer drugs, Tarceva (erlotinib) and Sutent (sunitinib), can defeat both dengue and Ebola in mice.

The study, led by Shirit Einav from Stanford University School of Medicine, was published February 27, 2017, in the Journal of Clinical Investigation.

The West African Ebola epidemic, which began in March 2014, is the largest and most complex Ebola outbreak since the virus was first discovered in 1976. Although that epidemic has subsided, it could return at any time. As many as 100 million people become infected with dengue virus each year. The dengue virus has 4 subtypes, which hampers the development of a vaccine. Moreover, a secondary infection by a different subtype can cause severe disease.

Emerging viral infections constitute a great threat to global health. Despite years of efforts to combat Ebola and dengue viruses, there is still a lack of effective vaccines and therapies. In this study, Einav and co-workers described the mechanism that Tarceva and Sutent use to disable viruses. They believed that the mechanism may also have implications in other infectious diseases.

By accessing publicly available databases, Einav's team found that Tarceva and Sutent impede the action of a couple of enzymes, AAK1 and GAK, in our bodies. The two enzymes can change the molecular makeup of cells in a way that causes them to bind more tightly to viruses. So AAK1 and GAK have been suggested as antiviral targets.

In previous research, the team discovered that Tarceva/Sutent combination is effective against HCV in a lab dish. For this work, they investigated whether the drug combination can defeat dengue and Ebola viruses, and found that the drug combination greatly improved the survival of mice infected with either virus. In summary, the findings suggest that repurposing existing drugs may be an approach to combat emerging viral infections.
 
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