You Can Help Cure Ebola!

 

By  Jesica Levingston Mac leod, PhD

Since the start of the outbreak last March, Ebola virus has already taken more than 8.000 lives and infected more than 21.200 people, according to the  Center for Disease Control (CDC). The panic raised from this situation rushed the testing of therapies to stop the outbreak and the research on the Ebola virus has seen a rebirth. Some research groups that have been working in this field for a long time can now openly ask for help. One of these groups is the one lead by Dr. Erica Ollman Shaphire at The Scripps Research Institute, California. In 2013 they published in Cell an analysis of the different conformations of Ebola VP40 (Viral Protein 40) aka the shape-shifting “transformer” protein. They reported 3 different conformations of this protein, and how this variety allows it to achieve multiple functions in the viral replication circle. This Ebola virus protein along with the glycoprotein would be used as target for anti viral research. In order to find new anti-virals, their approach is an in-silico scrutiny of thousands of compounds, using viral protein crystal structures in the in silico docking to find leads that may be tested in the lab as inhibitors. IBM is already helping them in this project, generating the World Community Grid to find drugs through the Outsmart Ebola Together project.  Here is where you can start helping, as this project involves a huge amount of data and computing time, they need volunteers that can donate their devices spare computing time (android, computer, kindle fire, etc) to generate a faster virtual supercomputer than can accelerate the discover of new potential drugs. This approach has been shown to be successful for other diseases like HIV and malaria, so you are welcome to join the fight against Ebola virus: https://secure.worldcommunitygrid.org/research/oet1/overview.do.

If you do not have any of these devices (I hope you are enjoying the public library free computers), you can still help Dr. Shapire quest to discover new therapies against Ebola. Her group is now “working to support the salary of a computer scientist to help process the data we are generating with the world community grid” as she describes it. To help identify the most promising drug leads for further testing you can donate money on: www.crowdrise.com/cureebola.

Other groups that were mostly working on other viruses, like Flu, also joined the race to discover efficient therapies. For example, last month, the Emerging Microbes and Infections journal of the Nature Publishing Group published the identification of 53 drugs that are potential inhibitors of the Ebola virus. One of the authors of this paper is Dr. Carles Martínez-Romero, from Dr. Adolfo García-Sastre’s lab in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai. In the study, Dr. Martínez-Romero and collaborators described how they narrowed the search from 2.816 FDA approved compounds to 53 potential antiviral drugs. This high-throughput screening was possible thanks to the use of the Ebola viral-like particle (VLP) entry assay. This allows studying Ebola viral entry without using the ”real”, full replicative virus. These 53 compounds blocked the entry of Ebola VLPs into the cell. Understanding how these market-ready compounds can inhibit Ebola entry and its infectious cycle will pave the way for a new generation of treatments against Ebola virus-associated disease.

Dr. Martínez-Romero had an early interest in science; “Since I was a child, I showed great interest in biological sciences and a great desire to question and discover. This led me to pursue my studies in Biotechnology in order to become a successful researcher.”Viruses are very interesting to me because, although they are not strictly living organisms, they are as old as life itself. Even though they are the origin of many illnesses in mammals and other organisms alike, we are tightly interconnected with viruses and they will continue shaping our evolution throughout the years to come.

I also asked him about advice to his fellow researchers, and he answered: “There is a famous quote of Dr. Albert Einstein: “If we knew what we were doing, it wouldn’t be called Research”. As postdocs and researchers in general, we are constantly pursuing new hypotheses. It is a very arduous path with its ups and downs but full of rewards and new challenges ahead.” About the future of the antiviral research, he keeps a positive view: “Several antiviral therapies are being developed to combat the current Ebola outbreak, such as antibody cocktails (Zmapp), antiviral drugs, and specific Ebola vaccines. Together with re-purposing screens like the one we published, a combination of therapeutic drugs can be used to obtain better antiviral strategies against the Ebola virus.”

Why Panic Can Accelerate the Therapies Discovery

 

Jesica Levingston Mac leod, PhD

 

In March, the Center of Disease Control (CDC) reported an outbreak of a “more virulent” Ebola virus infection in Guinea and Sierra Leone .Now, the disease has been spread to Liberia and Nigeria, among other West Africa countries. The final count is more than 1600 confirmed cases of Ebola hemorrhagic fever, with almost 900 deaths caused for this syndrome. Some of these cases included health-care workers. Indeed, two medical doctors were taken back to US to be treated with a new cocktail in the Emory University Hospital facilities in Atlanta, GA. Some Americans began to panic, for example Jon Stewart said in his show that “They are importing Ebola”.

Last week, two patients with Ebola like symptoms were all over the news. One of these cases happened in the New York City Mount Sinai Hospital, and the patient was isolated and tested right away. The hospital sent an email to all the employees updating them about the situation, and the press took over it. The bright side of the situation, in addition to the negative test result for Ebola virus, was the fast reply. The dark side was the paranoia and the lack of information and knowledge about this virus from the Manhattan community. It was alarming to read that some neighbors did not want to go to the emergency room in the hospital for fear to get infected. Well, you can’t get infected just for seating next to a sick person, or talk, or shake your hands: it is not an airborne transmitted virus.

The other problem is that the symptoms are pretty similar to other more “common” diseases: Fever, rash, severe abdominal pain, vomiting, and bleeding, both internally and externally. The difference is that the fatality rate is more than 60%. The transmission of the virus mostly occurs by contact with infected blood, secretions or organs of either bats, nonhuman primates or humans. This is why you should not eat bats or monkeys if you visit any of the affected areas, or hang around any cemeteries. Not surprisingly, Ebola was named as the most frightening disease in the world. It was documented for the first time in 1976 in the Republic of Congo; one of the sources came from the Ebola River.

 

In 2012 an outbreak in Uganda found us in a similar medical emptiness: the research of two of the vaccines that were “apparently” going great had been canceled by the department of defense, due to funding constraints. Therefore, so far we do not have any vaccine or effective treatment available.

In 2009, Dr. Feldmann, by then working in Canada (now in Montana, US), developed a vaccine that was used years after in Germany when a researcher accidentally pricked her finger with a syringe containing Ebola The Feldmann’s vaccine consists in a recombinant vesicular stomatitis virus expressing the Ebola glycoprotein which protects macaques from Ebola virus infections; although this method is not licensed for human use and the government founding has been random. A similar vaccine has been produce by Profectus BioSciences in Tarrytown, New York, but they are also short in the monetary founding that will push the research to the human trials.

The famous ZMapp serum, the treatment that the 2 Americans are receiving, is a cocktail of humanized, three-monoclonal- antibodies. This “cure” was the result of the collaboration of 25 laboratories among seven countries. The project, funded by the National Institute of Allergy and Infectious Diseases (NIAID), has a total budget of $28 millions. The scientific leader is the Dr. Erica Ollmann-Shapire, whom claimed that she would take the cocktail without doubts if she would be infected. Also the company Mapp Biopharmaceutical, based in California, is the principal producer of these antibodies. The initial trials in macaques were very successful, but the approval for the use in human trial is pending until 2015.

A lot of laboratories along the world are working towards the better understanding of the Ebola virus and the possible vaccines and cures. Most of these researches are founded by the US Department of Defense. But, why does the US Department of Defense care about an African virus? The answer is pretty obvious: it can be used as a bio hazard weapon. On the other hand, no leading pharmaceutical is going to invest in a “very expensive and time consuming” vaccine development to be used in countries that can’t afford even a basic level of health care. Some compounds are showing a promising antiviral effect in vitro and/or an inhibition of a variety of viral proteins activities. Sadly, all of them are in an early stage of drug development. On the other hand,the actual need for a therapy and a vaccine to stop this outbreak is speeding the drug development process.

 

Before freaking out, the best prevention method against this scaring virus is knowledge, so check out the updates in the CDC website.

Ebola – Closer than You Think

 

Ebola, the hemorrhagic fever is closer than you think, but there is no reason to panic…yet!

By Jesica Levingston Mac leod, PhD

In case you did not hear about it, the Center of Disease Control (CDC) reported an outbreak of a “more virulent” Ebola virus infections in Guinea, spreading now to Sierra Leone . Ebola virus is the etiological agent of severe hemorrhagic fever. The symptoms? Fever, rash, severe abdominal pain, vomiting, and bleeding, both internally and externally. The fatality rate? Around 90%. Even worse, these outbreaks are occurring with increasing frequency. Some explanations for this are the increased contact between humans and the natural reservoir of the viruses (fruit bats), and fluctuations in viral load and prevalence in this reservoir. The transmission of the virus mostly occurs by contact with infected blood, secretions or organs of either bats, nonhuman primates or humans. This is why you should not eat bats or monkeys if you visit any of the affected areas, or hang around any cemeteries. Not surprisingly, Ebola was named as the most frightening disease in the world. It was documented for the first time in 1976 in the Republic of Congo; one of the sources came from the Ebola River.

 

In 2012 an outbreak in Uganda found us in a similar medical emptiness: the research of two of the vaccines that were “apparently” going great had been canceled by the department of defense, due to funding constraints.  Therefore, so far we do not have any vaccine or effective treatment available.

 

Albeit a DNA based vaccine was described in 2003 to fully protected macaques against the fatal virus, it did not continue to further clinical trials.  It was not until 10 years later that a group in the US National Institutes of Health published research about a vaccine consisting of a recombinant vesicular stomatitis virus expressing the ebola glycoprotein which protects macaques from Ebola virus infections, although this method is not licensed for human use.

 

But, why does the US department of defense care about an African virus? The answer is pretty obvious: it can be used as a bio hazard weapon. On the other hand, no leading pharmaceutical is going to invest in a “very expensive and time consuming” vaccine development to be used in countries that can not afford even a basic level of health care. Some compounds are showing a promising antiviral effect in vitro and/or an inhibition of a variety of viral proteins activities. Sadly, all of them are in an early stage of drug development.

 

Before freaking out, the best “cure” and prevention method against this scaring virus is knowledge, so check out the updates in the CDC website.

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