Traditional Chinese medicine and Western science come together once again. Stephania tetranda is an herb that the Chinese have used to treat hypertension for many years. Now, researchers at Texas Biomedical Research Institute (TBRI) have discovered that a component of this herb, tetrandrine, can also be used to stop the Ebola Virus Disease, published today in the journal Science.
Over the past 11 months, more than 9,600 people have died from Ebola, mostly in West Africa. And though it’s slipped from the Western news media, the outbreak continues on in Guinea, Liberia, and Sierra Leone. The hunt has been on for both a vaccine to prevent and potential therapies to treat Ebola, but these have proven elusive. Filoviruses vary substantially, and each strain of Ebola is different. While some individuals treated in the U.S. received experimental therapies, they also received immune serum (antibodies from people who had recovered from Ebola). The data are not sufficient to determine if these have been effective. While Ebola is relatively rare, when it does strike, it’s extremely lethal: nearly 50% of people infected will die.
The story of tetrandrine starts before 2008, when Dr. Robert Davey (pictured above), Ewing Halsell Scholar in the Department of Immunology and Biology at TBRI, began studying the virus in the BSL-4 lab at TBRI right here in San Antonio. One of only five such laboratories in the U.S. and the only one privately operated, the TBRI BSL-4 lab is perhaps the smallest but most efficient of all. Built in 2000, this lab is for the “hot zone” diseases – those highly lethal agents for which there are no vaccines or cures. Incidentally, because this lab exists in San Antonio, University Hospital is perhaps one of the best equipped in the country to handle a patient with a deadly exotic virus: they plan and prepare should there ever be an accidental infection at TBRI. To date, there have been none.
Ebola virus was first identified in 1976, but understanding the complexities of the virus have proven difficult. When Davey came to TBRI, his team studied the proteins which enabled Ebola virus to infect a mammalian cell. In a paper published in 2008, they discovered that calcium channels were involved in infection. So they spent the next five years studying drugs that blocked these channels. Nada. Davey and his collaborators knew how Ebola contacted the cell and was swallowed up by the cell, but not how the virus moved across the cell.
Two Pore Channels
The researchers then discovered TPCs or “Two Pore Channels.” Little was known about these cellular channels, and most of what we know now is in part due to these experiments with Ebola virus. The virus meets the cell, becomes engulfed in a “bubble,” which then swallows it. Now it needs to traverse the cellular highway, but for that it needs TPCs. The TPCs “drive the bubble,” which ultimately leads to illness. All this happens before a person realizes they are sick.
But if the TPCs are blocked, that bubble with the virus is stopped dead in its tracks. It has no where to go. The key, then, was to find the compound which could block those TPCs. Enter tetrandrine, our Chinese herbal remedy for hypertension. Along with their collaborators in Munich, Germany and at Southwest Research Institute (SWRI), the teams found that Tetrandrine acts as a traffic cop to that bubble driving the virus across the cell. Tetrandrine says “Stop!” and the virus has nowhere to go and dies.
Davey and his colleagues found that mice with no TPCs did not become sick from Ebola. Further studies showed that once “normal” mice infected with Ebola virus, treatment with Tetrandrine prevented the mice from becoming sick.
The trick in treatment, always, is to find a drug that will kill the bad stuff, without hurting the patient too much. Tetrandrine has minimal side effects and requires a small dosage to be effective, making it an ideal drug candidate. Now it must be tested in an animal model which mimics human disease. Meanwhile teams from TBRI and SWRI in San Antonio and other teams from Germany and Japan are working together to identify related compounds.
A new drug, for whom?
A new test kit for Ebola is able to identify a viral infection rapidly, but only after the patient develops symptoms. Initial studies with tetrandrine suggest that it’s most effective if used early in the disease process, before obvious symptoms have occurred. As clinicians treating Ebola patients are at highest risk (it’s called the “Nurse Killer” in some parts of West Africa), the most likely use will be prophylactic, that is, taking the drug if you treat Ebola patients, thereby minimizing risk of illness if the clinician becomes infected.
It took seven years to get to this point. Do we have another seven to have an FDA approved treatment? Scientific advances tend to be exponential so it’s possible we could have a safe and effective treatment in two to five years, too late for the current outbreak, but hopeful for the future.
*Featured/top image: Dr. Robert Davey and Yasuteru Sakurai examine samples at Texas Biomedical Research Institute. Courtesy photo.