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  • richardmitnick 3:46 pm on October 6, 2015 Permalink | Reply
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    From Outsmart Ebola Together at WCG: “Finding new avenues to attack Ebola” 

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    6 Oct 2015
    Dr. Erica Ollmann Saphire, PhD, The Scripps Research Institute

    Summary
    Efforts to simulate matches between candidate compounds and one key Ebola virus protein are largely complete. Simulations of matches against another, newly discovered target protein are beginning now. Even as simulation work continues, the team is beginning to analyze these results and home in on compounds that could form the basis for effective new drugs against Ebola and other related diseases. Thanks to your help, and a new grant, the work is proceeding well.

    1
    Two Protein Data Bank structures for the ribonuclease H domain of HIV reverse transcriptase. We used structural and experimental data for this domain to optimize our analysis protocols for the Lassa NP exonuclease site.

    Thanks to the efforts of thousands of World Community Grid members, my team has continued to make progress on Outsmart Ebola Together, a project whose goal is to find new drugs for curing Ebola and related life-threatening viral hemorrhagic fevers.

    Outsmart Ebola Together began with a study of potential drug attacks against the receptor-binding site of the Ebola surface glycoprotein (GP). We then announced the start of work on a second drug target: the nucleoprotein (NP) of Lassa Fever virus. Specifically, we are looking for drugs that attack the newly discovered “exonuclease site” of Lassa NP. This exonuclease site helps conceal the virus’s presence from the infected human cell by destroying the virus’s own excess production of double-stranded RNA.

    We have since prepared research tasks for testing the Lassa NP exonuclease site against millions of potential drugs. These tasks are now ready for use, and will be sent out to World Community Grid volunteers over the coming months.

    Our lab has also been investigating the Ebola NP and VP35 proteins. NP and VP35 must engage in a series of specific interactions with each other as Ebola virus replicates. These newly discovered interactions could potentially be disrupted by new drugs, making NP and VP35 possible future targets for investigation by Outsmart Ebola Together.

    At this stage in the project, we’ve gathered enough data that we need to begin focusing on analysis procedures for the data already returned by World Community Grid volunteers. We must analyze the data for both the Ebola GP receptor-binding site and the Lassa NP exonuclease site; and our analysis procedures must be sufficient to filter out false positives from the large quantity of results returned.

    For each viral protein site that we test against potential drugs, we assure the validity of our analysis as follows: We select a substantially analogous site (generally from a different virus) for which there exists experimental data about potential drugs that bind or do not bind to the site. We then tune our analysis protocols so that, when applied to this site, our analysis results closely match the known experimental results. Only when this is done do we feel that we can confidently apply the same analysis protocols to the site of current interest.

    In particular, this summer we looked closely at analysis optimization for the Lassa NP exonuclease site. As the analogous well-studied site, we chose the “ribonuclease H domain” of HIV reverse transcriptase, which has strong similarities to the Lassa NP exonuclease site in its protein structure and use of catalytic metal ions. The optimization of our analysis protocols against experimental data for the HIV ribonuclease H domain is now complete, and we are looking forward to the arrival of the Lassa NP exonuclease data as it is processed by World Community Grid volunteers. Candidate drugs that pass the analysis stage will go on to a next round of experiments, conducted in the lab rather than by computer simulation.

    We are also happy to announce that a $50,000 grant to support this work has been provided by the Robert Wood Johnson Foundation President’s Grant Fund of the Princeton Area Community Foundation. With this grant and the vast computing resources of World Community Grid, our way to the successful completion of the project is clear.

    As always, we close with a thank-you to the volunteers who have run this work for us. As you can see, we’ve already made significant progress but there is much work still to do. Make sure you’re signed up to contribute to this project, and spread the word about our lifesaving work!

    See the full article here.

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    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”

    WCG projects run on BOINC software from UC Berkeley.

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

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    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!

    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-
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  • richardmitnick 11:15 am on October 3, 2015 Permalink | Reply
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    From Oxford: “Behind the scenes of creating the ground-breaking Ebola vaccine” 

    U Oxford bloc

    Oxford University

    Professor Adrian Hill of Oxford’s Jenner Institute led the first clinical trial of a successful Ebola virus vaccine last year. To target the outbreak his remarkable team compressed a process that takes six months into six weeks.

    1

    The recent Ebola outbreak was the deadliest since the virus’ discovery in the 1970s. Fortunately Professor Adrian Hill, Director of Oxford’s Jenner Institute, and his team managed to create a vaccine response in record time.

    At his Alumni Weekend talk, Professor Hill described the desperate situation that West Africa was in last year. Ebola was in the news every day, with death tolls spiralling up through the summer. There were no vaccines known to protect against Ebola, or drugs to treat those infected at the time. Promising vaccine candidates did exist in the US, but only one had been tested in humans and had been subsequently abandoned.

    Usually Ebola outbreaks have been contained using the traditional methods of containment in Central Africa, but it was spreading through the continent rapidly – in Guinea, Sierra Leone, and Liberia – in 2014. With no vaccines ready to be tested out in West Africa the situation was grave, Professor Hill explained.

    2

    The resulting ambitious trial at Oxford was funded by the Wellcome Trust, Medical Research Council and Department for International Development. Phase one began in mid-September 2014 with 60 volunteers, and a further 80 out in Mali in October – after the team was swamped with volunteers anxious to help.

    For the successful vaccine Professor Hill’s team used a single Ebola gene in a chimpanzee adenovirus to generate an immune response. As it did not contain any infectious virus material, it did not cause the patient to become infected. The trial’s efficiency exceeded all expectations, with a novel vaccine ready from the trial to finished product in nine months.

    3

    The researchers then used an innovative trial design in West Africa, in which the family, friends and contacts in a ‘ring’ around an Ebola patient would be given the vaccine. In March 2015, the first infected individuals were identified and the ring vaccination began in Guinea, which continues to have the majority of cases. Both this ‘ring’ approach and the vaccine were a great success.

    Looking to the future, Professor Hill reflected that it would be wonderful if Britain could manufacture vaccines ‘on a significant scale’ once again. David Cameron has promised £20million to protect Britain from future pandemics this year, but how that money will be allocated has not yet been decided.

    Professor Hill explained more broadly the challenges left facing vaccination development. On the positive side, only two countries in the world are left with polio, and smallpox has been eradicated. This leaves the big three vaccinations to find as HIV/AIDS, malaria, and an improved TB jab.

    In terms of Ebola itself, the vaccine that Professor Hill’s team worked on was for the Zaire strain, but there still remains to be one for the Sudan strain. He pointed out that there will ‘almost certainly’ be more major outbreaks, especially as Africa’s population increases, people travel more and cities expand.

    For all of the team’s hard work, the University decided that their contributions should be recognised, and commissioned a University of Oxford Ebola medal this summer. The medals were presented by the Vice-Chancellor, Professor Andrew Hamilton, and the head of the Nuffield Department of Clinical Medicine, Professor Peter Ratcliffe. Professor Hamilton reflected: ‘The work of the team was absolutely critical. These kinds of outbreaks can arise at any time and we need to be ready to respond. They responded magnificently.’

    For further details about the Jenner Institute click here.

    Photographs courtesy of Oxford University Images

    See the full article here.

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    U Oxford campus

    Oxford is a collegiate university, consisting of the central University and colleges. The central University is composed of academic departments and research centres, administrative departments, libraries and museums. The 38 colleges are self-governing and financially independent institutions, which are related to the central University in a federal system. There are also six permanent private halls, which were founded by different Christian denominations and which still retain their Christian character.

    The different roles of the colleges and the University have evolved over time.

     
  • richardmitnick 6:26 am on August 18, 2015 Permalink | Reply
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    From MIT: “Quick test for Ebola” 


    MIT News

    February 24, 2015
    Anne Trafton

    1
    A new paper diagnostic device can detect Ebola as well as other viral hemorrhagic fevers in about 10 minutes. The device (pictured here) has silver nanoparticles of different colors that indicate different diseases. On the left is the unused device, opened to reveal the contents inside. On the right, the device has been used for diagnosis; the colored bands show positive tests. Photo courtesy of Jose Gomez-Marquez, Helena de Puig, and Chun-Wan Yen

    When diagnosing a case of Ebola, time is of the essence. However, existing diagnostic tests take at least a day or two to yield results, preventing health care workers from quickly determining whether a patient needs immediate treatment and isolation.

    A new test from MIT researchers could change that: The device, a simple paper strip similar to a pregnancy test, can rapidly diagnose Ebola, as well as other viral hemorrhagic fevers such as yellow fever and dengue fever.

    “As we saw with the recent Ebola outbreak, sometimes people present with symptoms and it’s not clear what they have,” says Kimberly Hamad-Schifferli, a visiting scientist in MIT’s Department of Mechanical Engineering and a member of the technical staff at MIT’s Lincoln Laboratory. “We wanted to come up with a rapid diagnostic that could differentiate between different diseases.”

    Hamad-Schifferli and Lee Gehrke, the Hermann L.F. von Helmholtz Professor in MIT’s Institute for Medical Engineering and Science (IMES), are the senior authors of a paper describing the new device in the journal Lab on a Chip. The paper’s lead author is IMES postdoc Chun-Wan Yen, and other authors are graduate student Helena de Puig, IMES postdoc Justina Tam, IMES instructor Jose Gomez-Marquez, and visiting scientist Irene Bosch.

    Color-coded test

    Currently, the only way to diagnose Ebola is to send patient blood samples to a lab that can perform advanced techniques such as polymerase chain reaction (PCR), which can detect genetic material from the Ebola virus. This is very accurate but time-consuming, and some areas of Africa where Ebola and other fevers are endemic have limited access to this kind of technology.

    The new device relies on lateral flow technology, which is used in pregnancy tests and has recently been exploited for diagnosing strep throat and other bacterial infections. Until now, however, no one has applied a multiplexing approach, using multicolored nanoparticles, to simultaneously screen for multiple pathogens.

    “For many hemorrhagic fever viruses, like West Nile and dengue and Ebola, and a lot of other ones in developing countries, like Argentine hemorrhagic fever and the Hantavirus diseases, there are just no rapid diagnostics at all,” says Gehrke, who began working with Hamad-Schifferli four years ago to develop the new device.

    Unlike most existing paper diagnostics, which test for only one disease, the new MIT strips are color-coded so they can be used to distinguish among several diseases. To achieve that, the researchers used triangular nanoparticles, made of silver, that can take on different colors depending on their size.

    The researchers created red, orange, and green nanoparticles and linked them to antibodies that recognize Ebola, dengue fever, and yellow fever. As a patient’s blood serum flows along the strip, any viral proteins that match the antibodies painted on the stripes will get caught, and those nanoparticles will become visible. This can be seen by the naked eye; for those who are colorblind, a cellphone camera could be used to distinguish the colors.

    “When we run a patient sample through the strip, if you see an orange band you know they have yellow fever, if it shows up as a red band you know they have Ebola, and if it shows up green then we know that they have dengue,” Hamad-Schifferli says.

    This process takes about 10 minutes, allowing health care workers to rapidly perform triage and determine if patients should be isolated, helping to prevent the disease from spreading further.

    Warren Chan, an associate professor at the University of Toronto Institute of Biomaterials and Biomedical Engineering, says he is impressed with the device because it not only offers faster diagnosis, but also requires smaller patient blood samples, as just one test strip can detect multiple diseases. “It’s a step up from what everyone else is doing,” says Chan, who was not involved in the research. “They’re targeting diseases that are really relevant to what’s going on in the world at this point, and have shown that they can detect them simultaneously.”

    Faster triage

    The researchers envision their new device as a complement to existing diagnostic technologies, such as PCR.

    “If you’re in a situation in the field with no power and no special technologies, if you want to know if a patient has Ebola, this test can tell you very quickly that you might not want to put that patient in a waiting room with other people who might not be infected,” says Gehrke, who is also a professor of microbiology and immunology at Harvard Medical School. “That initial triage can be very important from a public health standpoint, and there could be a follow-up test later with PCR or something to confirm.”

    The researchers hope to obtain Food and Drug Administration approval to begin using the device in areas where the Ebola outbreak is still ongoing. In order to do that, they are now testing the device in the lab with engineered viral proteins, as well as serum samples from infected animals.

    This type of device could also be customized to detect other viral hemorrhagic fevers or other infectious diseases, by linking the silver nanoparticles to different antibodies.

    “Thankfully the Ebola outbreak is dying off, which is a good thing,” Gehrke says. “But what we’re thinking about is what’s coming next. There will undoubtedly be other viral outbreaks. It might be Sudan virus, it might be another hemorrhagic fever. What we’re trying to do is develop the antibodies needed to be ready for the next outbreak that’s going to happen.”

    The research was funded by the National Institute of Allergy and Infectious Disease.

    See the full article here.

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  • richardmitnick 1:05 pm on July 31, 2015 Permalink | Reply
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    From New Scientist- “Ebola vaccine success: Race is now on to protect those at risk” 

    NewScientist

    New Scientist

    31 July 2015
    No Writer Credit

    1
    A vaccine can now protect against Ebola (Image: Cellou BinaniI/AFP/Getty Images)

    A vaccine for Ebola produced in just one year instead of the usual decade provides 100-per-cent protection against the disease. Preparations are already under way to make it available to healthcare workers and families wherever the virus remains at large.

    “This is a very good day,” says Seth Berkley, chief executive of the GAVI Alliance, the global organisation that has earmarked $390 million to extend availability of the VSV-ZEBOV vaccine beyond Guinea, the country where it has been successfully tested on more than 7500 people.

    The epidemic is now largely under control, but there have been 28,000 cases leading to 11,000 deaths in Guinea, Sierra Leone and Liberia. But cases are still coming to light, and the virus is still at large, lurking in the body fluids of survivors for as long as 6 months.

    “All affected countries should immediately start and multiply ring vaccinations to break chains of transmission and vaccinate all frontline workers to protect them,” says Bertrand Draguez, medical director of relief organisation Médecins Sans Frontières.

    The rapid availability of a vaccine would be a huge boost for citizens of those three countries and for all the health workers still operating in them to deal with new cases.

    Emergency authorisation

    Berkley says that the GAVI Alliance has already earmarked “considerable” funds that could make this roll out possible, and that discussions are under way with the governments of affected countries, the funders of the clinical trials, the manufacturer of the vaccine and the World Health Organization to decide how to move forward as fast as possible.

    Although the trial isn’t yet over, the WHO could theoretically issue an Emergency Use Authorisation before it ends. This would enable the vaccine to be legally deployed where needed.

    “When there’s a WHO recommendation, we will be willing to purchase and stockpile the vaccine until we get regulatory authorisation from individual governments,” Berkley says.

    The trial is still in progress, but evidence that the vaccine works arose by studying how well the vaccine protected health workers and family members associated with new cases of Ebola. They wanted to see how well this strategy of “ring vaccination” – immunising those people in closest contact with any new cases – protected those exposed.

    Rather than vaccinating only half the participants, and risking the lives of others by giving them a dummy vaccine, the researchers gave half the participants the vaccine immediately after they had contact with a newly diagnosed case, while the other half received it three weeks later.

    After three months, the result was resounding. No instant recipients were infected, but 16 of those receiving the vaccine three weeks later were. “This is an extremely promising development,” said Margaret Chan, director-general of the WHO. The results at three months were so impressive that all subsequent participants have since been receiving the vaccine immediately.

    Hard to store

    Developed initially by the Public Health Agency of Canada, the vaccine is a live but harmless virus called vesicular stomatitis virus, which normally infects animals, engineered to contain a key fragment from the Ebola virus. The immune systems of recipients make antibodies that prime for defence against the real virus.

    The race is now on to provide it wherever possible, pending negotiations between all the parties involved. “We can say that Guinea is now taken care of, but what happens in Sierra Leone and Liberia, and other countries where there are outbreaks such as Mali and Uganda,” says Berkley. “We need some type of procedure to say it’s OK to use it in these other settings.”

    Berkley said that the vaccine is not perfect. It must be stored at -80 °C, which is not easy to guarantee in tropical countries. It also may not protect against all strains of Ebola. Nor is it yet established how long immunity lasts.

    But other trials of vaccines against ebola are under way, says Margaret Harris of the WHO. In Liberia, the VSV-ZEBOV vaccine is being trialled head-to-head against a rival vaccine produced by Glaxo-Smith Kline, and a vaccine developed by the US Centers for Disease Control and Prevention in Atlanta, Georgia, is being tested in Sierra Leone.

    Harris said that cases are still coming to light, but they are waning in number. “We’ve had a very encouraging week, and for the first time we’ve seen a column of zeros where there are usually new cases.”

    See the full article here.
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  • richardmitnick 2:47 pm on March 26, 2015 Permalink | Reply
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    From Wisconsin: “Ebola whole virus vaccine shown effective, safe in primates” 

    U Wisconsin

    University of Wisconsin

    March 26, 2015
    Terry Devitt

    1
    Ebola virus swarms the surface of a host cell in this electron micrograph. Like most viruses, Ebola requires the help of a host cell to survive and replicate. Photo: Takeshi Noda, University of Tokyo

    An Ebola whole virus vaccine, constructed using a novel experimental platform, has been shown to effectively protect monkeys exposed to the often fatal virus.

    The vaccine, described today (March 26, 2015) in the journal Science, was developed by a group led by Yoshihiro Kawaoka, a University of Wisconsin-Madison expert on avian influenza, Ebola and other viruses of medical importance. It differs from other Ebola vaccines because as an inactivated whole virus vaccine, it primes the host immune system with the full complement of Ebola viral proteins and genes, potentially conferring greater protection.

    “In terms of efficacy, this affords excellent protection,” explains Kawaoka, a professor of pathobiological sciences in the UW-Madison School of Veterinary Medicine and who also holds a faculty appointment at the University of Tokyo. “It is also a very safe vaccine.”

    The vaccine was constructed on an experimental platform first devised in 2008 by Peter Halfmann, a research scientist in Kawaoka’s lab. The system allows researchers to safely work with the virus thanks to the deletion of a key gene known as VP30, which the Ebola virus uses to make a protein required for it to reproduce in host cells. Ebola virus has only eight genes and, like most viruses, depends on the molecular machinery of host cells to grow and become infectious.

    By engineering monkey kidney cells to express the VP30 protein, the virus can be safely studied in the lab and be used as a basis for devising countermeasures like a whole virus vaccine. The vaccine reported by Kawaoka and his colleagues was additionally chemically inactivated using hydrogen peroxide, according to the new Science report.

    Ebola first emerged in 1976 in Sudan and Zaire. The current outbreak in West Africa has so far claimed more than 10,000 lives. There are no proven treatments or vaccines, although several vaccine platforms have been devised in recent years, four of which recently advanced to the clinical trial stage in humans.

    2
    Yoshihiro Kawaoka

    The new vaccine reported by Kawaoka has not been tested in people. However, the successful tests in nonhuman primates conducted at the National Institutes of Health (NIH) Rocky Mountain Laboratories, a biosafety level 4 facility in Hamilton, Montana, may prompt further tests and possibly clinical trials of the new vaccine. The work at Rocky Mountain Laboratories was conducted in collaboration with a group led by Heinz Feldmann of NIH.

    Those studies were conducted with cynomolgus macaques, which are very susceptible to Ebola. “It’s the best model,” Kawaoka says. “If you get protection with this model, it’s working.”

    Ebola vaccines currently in trials include:

    A DNA-based plasmid vaccine that primes host cells with some of the Ebola proteins.
    A vaccine based on a replication incompetent chimpanzee respiratory virus engineered to express a key Ebola protein.
    A live attenuated virus from the same family of viruses that causes rabies, also engineered to express a critical Ebola protein.
    A vaccine based on a vaccinia virus and engineered to express a critical Ebola protein.

    Each of those strategies, Kawaoka notes, has drawbacks in terms of safety and delivery.

    Whole virus vaccines have long been used to successfully prevent serious human diseases, including polio, influenza, hepatitis and human papillomavirus-mediated cervical cancer.

    The advantage conferred by inactivated whole virus vaccines such as the one devised by Halfmann, Kawaoka and their colleagues is that they present the complete range of proteins and genetic material to the host immune system, which is then more likely to trigger a broader and more robust immune response.

    Early attempts to devise an inactivated whole virus Ebola vaccine through irradiation and the preservative formalin failed to protect monkeys exposed to the Ebola virus and were abandoned.

    Although the new vaccine has surpassed that hurdle, human trials are expensive and complex, costing millions of dollars.

    The Ebola vaccine study conducted by Kawaoka was supported by the National Institutes of Health and by the Japanese Health and Labour Sciences Research Grants.

    In addition to Kawaoka, co-authors of the new Science report include Halfmann, Lindsay Hill-Batorski and Gabriele Neumann of UW-Madison and Andrea Marzi, W. Lesley Shupert and Feldmann of the National Institute of Allergy and Infectious Diseases.

    See the full article here.

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    In achievement and prestige, the University of Wisconsin–Madison has long been recognized as one of America’s great universities. A public, land-grant institution, UW–Madison offers a complete spectrum of liberal arts studies, professional programs and student activities. Spanning 936 acres along the southern shore of Lake Mendota, the campus is located in the city of Madison.

     
  • richardmitnick 7:10 am on March 12, 2015 Permalink | Reply
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    From AAAS: “New Ebola drug trial starts in Sierra Leone” 

    AAAS

    AAAS

    11 March 2015
    Kai Kupferschmidt

    1
    The Ebola treatment center in Kerry Town, Sierra Leone. (PO (Phot) Carl Osmond/MOD/Wikimedia Commons)

    Researchers in Sierra Leone today started a new phase II trial of an experimental drug in Ebola patients. The first participant received an injection of the therapeutic, called TKM-Ebola, this morning at an Ebola treatment unit in Port Loko*. The trial may expand to other sites; the study team hopes to have an answer fast so that it can either move on to another drug or start a phase III study of TKM-Ebola.

    Produced by Tekmira Pharmaceuticals in Burnaby, Canada, TKM-Ebola is made of synthetic, small interfering RNAs packaged into lipid nanoparticles. The RNAs target three of Ebola’s seven genes, blocking the virus’s replication. TKM-Ebola has been shown to work well in monkeys; the efficacy trial in humans is only starting now because there was not enough of the drug available earlier. Also, the RNAs have been adapted to the strain circulating at the moment.

    The study does not have a placebo arm; all patients at the trial site are eligible for the drug, and researchers hope to determine whether it works by comparing them with patients treated elsewhere.

    However, not every Ebola patient at the unit may actually get the drug because of practical reasons. The treatment is given as a 2-hour infusion every day for a week; patients need to be watched for 8 hours after the infusion because of worries that the drug could produce a dangerous inflammatory response known as a cytokine storm. Doctors and nurses can only spend so much time in their protective equipment in the tropical heat, which means they may not be able to serve everyone. “Staff have a very narrow window, and if there are several patients that are eligible in the morning, we have to choose one randomly,” says Trudie Lang, a global health researcher at the University of Oxford in the United Kingdom and one of the study’s leaders. Patients at the trial site who don’t receive the drug could also be used as controls in the study.

    The trial aims to enroll up to 100 patients, but Lang says that it may arrive at an answer much earlier. “We are looking for a big effect, and if there is a big yes or a big no, we hope to see that sooner.” If there is a clear signal that the drug does nothing, the team wants to try to test another experimental drug before Sierra Leone brings down the number of cases to zero. Neighboring Liberia has not seen new cases in more than 2 weeks; although Sierra Leone’s epidemic has slowed considerably, there are still about 10 new cases every day.

    If TKM-Ebola does seem to work, the team wants to go straight to a bigger phase III clinical trial. It’s “essential that we push forward with clinical trials while we still have a realistic chance of getting answers about which, if any, of the candidate treatments can save lives in this, and in future outbreaks,” said principal investigator Peter Horby in a statement released today by the Wellcome Trust, a charity that is funding the trial.

    In Liberia, Horby’s group had previously tested brincidofovir, a drug developed for cytomegalovirus and adenovirus that also showed anti-Ebola activity in the lab. That trial had to be stopped last month when Chimerix, the company producing the drug, withdrew their support. There were too few Ebola cases in Liberia, and the scientists weren’t able to expand the trial to Sierra Leone, Lang says. Only a handful of patients were treated; those data will be released in the coming months. “It will be important when we can step back from the business of running this trial to explore what went wrong and what went well in setting up trials during this epidemic,“ she says.

    So far, no drug has been proven to be effective against Ebola. A study of the Japanese influenza drug favipiravir is going on in Guinea, and scientists have reported a first weak signal that it may be helping some patients. A trial to use serum from recovered Ebola patients as a therapy for others is ongoing in Guinea, and the U.S. National Institutes of Health has said it is planning a trial of an antibody cocktail called ZMapp.

    *Update: This story originally said the trial had started in an Ebola treatment unit in Kerry Town, as its file in the Pan African Clinical Trials Registry indicated. It actually started in Port Loko and may be expanded later to Kerry Town.

    See the full article here.

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  • richardmitnick 1:25 pm on May 19, 2014 Permalink | Reply
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    From SLAC Lab: “Fighting Ebola Virus Disease: ‘Transformer’ Protein Provides New Insights” 


    SLAC Lab

    May 15, 2014
    Manuel Gnida

    A new study reveals that a protein of the Ebola virus can transform into three distinct shapes, each with a separate function that is critical to the virus’s survival. Each shape offers a potential target for developing drugs against Ebola virus disease, a hemorrhagic fever that kills up to 9 out of 10 infected patients in outbreaks such as the current one in West Africa.

    eb
    VP40, a protein of the Ebola virus, can arrange itself into three very different shapes, shown in blue, each with a distinct function. (Nikola Stojanovic/SLAC and Zachary Bornholdt/The Scripps Research Institute)

    ebola
    Each of VP40’s structural arrangements is linked to a different function in the virus life cycle. While traveling inside infected cells, VP40 assumes a butterfly shape (top). Near the cell nucleus, VP40 transforms into a ring (bottom left) that regulates how the viral genetic information is copied. At the cell membrane, VP40 assembles into a linear structure (bottom right), which plays a role in the creation of new viruses. (Erica Ollmann Saphire and Zachary Bornholdt/The Scripps Research Institute)

    At SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) and other X-ray facilities, a team led by Erica Ollmann Saphire of The Scripps Research Institute analyzed the structure of VP40, a protein best known for its role in creating and releasing new copies of the virus from infected cells.

    “The interesting thing about VP40 is that it does more than that,” Saphire says. “We found that it is multifunctional, with several essential roles for the virus.” The team reported its results in Cell.

    One Protein, Three Structures

    The team discovered that the protein can alter its shape, causing multiple copies of the protein to join up and create three very different assemblies: a butterfly shape composed of two, a ring formed by eight, and a linear structure built from six VP40 molecules. Prior to the study, only the protein ring was known.

    But what unique functions do the individual structures have? The researchers took the study to the next level by combining their X-ray data with additional biological experiments. “This approach allowed us to track not only where the different structures are located, but also what they do inside the cell,” Saphire says.

    It turns out that the function of each structure is linked to a specific stage of the virus life cycle.

    While moving around inside infected cells, VP40 assumes the butterfly shape.

    In the early stages of an infection, the VP40 molecules change their structure and assemble into a ring near the cell nucleus, regulating how the virus’s genetic information is copied.

    In the later stages, VP40 travels to the cell’s outer layer, or membrane, and transforms into its linear structure, which plays a crucial role in the creation of new copies of the virus.

    The transformational changes of VP40 update the nearly 60-year-old “central dogma of biology,” which implies that a given gene typically makes a single protein with a single 3-D shape. “Our findings open the central dogma wide up,” says Saphire, who suggests that structural rearrangements as seen in VP40 may be more common than previously thought.

    From an evolutionary perspective, structural diversity has developed out of necessity. Unlike humans, who possess some 20,000 protein-encoding genes, the Ebola virus must get by with a drastically smaller number.

    “The Ebola virus has only seven genes. However, its proteins must serve many more functions than that,” explains Scripps researcher Zachary Bornholdt, the study’s first author. “Protein transformability allows the virus to make the most out of very little.”

    Potential Drug Targets

    All three functions of VP40 – traveling inside infected cells, regulating genetic information and creating new viruses – are essential to the Ebola virus, and disrupting any of the corresponding structures or their transformations would severely affect it. Therefore, VP40’s triple role provides researchers with important clues for the development of potential antiviral drugs.

    “The more we are able to define VP40’s structures and functions, the more we can expand what we can do with this information,” Bornholdt says. “Our data suggest, for instance, that it might be more effective to target the ring than the other structures because only a small fraction of all VP40 molecules form the ring in the course of the viral life cycle.”

    Although a cure for Ebola virus disease is still remote, the new study already has practical applications: The same VP40 proteins produced for this study are being used in test strips to identify the disease in patients affected by the current outbreak in West Africa.

    The research team included scientists from The Scripps Research Institute and the University of Wisconsin-Madison in the U.S., as well as from the University of Tokyo and the Exploratory Research for Advanced Technology Program in Japan. Part of the research was performed at SSRL’s microbeam facility for crystallography (Beam Line 12-2). The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences.

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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