- Dengue and Ebola are serious illness caused by viral infections
- A drug combination can be used to inhibit Dengue and Ebola infections
- Erloitinib-sunitinib drug combination found to be effective when compared to taking it individually
Dengue and Ebola virus infections were inhibited by using a combination of two cancer drugs in mice, finds a research team from the Stanford University School of Medicine.
Around 390 million people in over 100 countries are affected with dengue annually. Four different strains of the dengue virus may exist which may make it difficult to develop a vaccine.
‘An anti-cancer drug combination of erloitinib-sunitinib can be used to defeat dengue and Ebola infections.’
The drug combinations which showed efficacy against hepatitis C virus were found to be effective even in Zika and West Nile virus. These viruses were somehow related to Hepatitis C virus. However, the infections caused by Dengue and Ebola viruses are totally different from each other.
The research study was published in the Journal of Clinical Investigation
. It mainly tried to focus on specific mechanism by which drugs can obstruct a number of RNA viruses.
Senior author, Shirit Einav, MD, assistant professor of infectious diseases and of microbiology and immunology, said, "We've shown that a single combination of drugs can be effective across a broad range of viruses -- even when those viruses hail from widely separated branches of the evolutionary tree."
The main reason behind how drugs are used to combat the infections by different viruses is that their disabling activity is targeted towards the proteins of the host cells and not on the virus, Einav, said.
Strategies to Combat RNA Virus
Dengue and Ebola infections are caused by RNA viruses that possess faulty replication process; This may cause errors due to genetic material and may result in mutations. Due to the changes in the genetic material they may quickly acquire resistance to an antiviral drug which targets a specific viral enzyme.
Einav, said, "The 'one drug, one bug' approach can be quite successful, as in the case of hepatitis C virus."
It nearly took more than 10 years of research and costs may exceed $2 billion to develop drugs. This may make it impossible for predicting the emerging viral threat.
"We're always getting blindsided," she said.
There is no proper antiviral drugs for treating Ebola and Dengue virus. Vaccine for Ebola virus may show promise in treatment, but is not yet approved. While the recently approved vaccine for dengue virus may show only limited efficacy. These secondary infections can be life-threatening.
Viruses are capable of hijacking the cell mechanisms. They are capable of moving through the bus which moves through the cell compartments. These buses are regulated by enzymes, especially the AAK1 and GAK enzyme which are capable of lowering the fares by binding them more strongly to the cargo.
Normally, Antiviral drugs may aim to disable a specific viral enzyme. However, the two drug-drug combinations which work against Ebola and Dengue which impedes AAK1's and GAK enzyme.
Erloitinib and sunitinib drugs are approved by the Food and Drug Administration for the treatment of cancer.
Drugs that have anti-cancer activity may neither target AAK1 or GAK enzyme activity. However, the two drugs may impair AAK1 and GAK activity.
The drug combination was tested for antiviral activity in the lab dishes with Ebola and Dengue.
Testing the Drug Combination
The research team has administered erloitinib-sunitinib drug combination to be taken once daily on the day of dengue-virus infections. The two drugs were given for five days at doses which were comparable to those approved against cancer in humans.
The control mice were found to die between days four and eight. However, 65-100% survived after treatment with drug combination. It was also noted that drugs were found to provide less protection when given individually.
During another experiment, the drug combination was also found to retain antiviral efficacy when given less than 48 hours after infection.
In an experiment with ebola virus, the drug was administered daily for 10 days by the scientists starting at 6 hours before infection. About 90% of the control mice died within two weeks.
About half of the mice which received the drug combination was found to survive. Even in this experiment, drug combination was found to be more effective than the individual drugs.
It was also found that the ability of the dengue virus to develop drug resistance was inhibited when drugs were given in a combination.
Advantages of Drug Combination
- No way for viral mutations to the alter the proteins in the cells.
- No way for the virus to mutate around the proteins.
The findings are also filed for patents on Intellectual property by the Stanford's Office of Technology licensing.