A pubmed literature search 1976 through october 20, 2014 was conducted using the search term ebola. These highlights are a snapshot of interesting research done across the field of chemical biology, and this months select features a new approach to targeting ras signaling, a discovery of a nucleoside analog as a protective agent against filovirus diseases, an application. The recent disastrous outbreak of ebola virus disease in west african nations and the emergence of merscov infection in the middle east underscore the importance and urgency of successful development. Pdf bcx4430 a broadspectrum antiviral adenosine nucleoside. Ebola virus causes evola virus disease evd or ebola hemorrhagic fever in human and nonhuman primates. Although the approval process for drugs and vaccines is. Galidesivir bcx4430 is an adenosine nucleoside analogue designed to inhibit viral rna. Discovering drugs for the treatment of ebola virus springerlink.
Bcx4430 a broadspectrum antiviral adenosine nucleoside analog under development for the treatment of ebola virus disease raymond taylor a, pravin kotiana, travis warrenb, rekha panchal b, sina bavarib, justin julanderc, sylvia dobo a, angela rosea, yahya elkattana, brian taubenheim d, yarlagadda babua, william p. The outbreakof the zaire species of ebola virus, which is the most virulentbegan in guinea in december 20, and spread mostly to liberia and sierra leone. Ebola virus, a member of the filoviridae family, is a causative agent of severe viral hemorrhagic fever in humans. Pdf background the recent reemergence of ebola virus in the democratic republic of the congo. Treatments for patients infected with the ebola virus are still in early stages of development, notes marco cavaleri, head of antiinfectives and vaccines at ema. The adenosine nucleoside analog bcx4430 is a directacting antiviral drug under.
Bcx4430 is a small molecule drug with recent nih support that, in. Some treatments such as mab114, regneb3, and bcx4430 showed tolerability. Ebola treatment centre etc, following two negative tests on serial laboratory specimens, on 12 june 2018. Tambien es importante avisar a las autoridades sanitarias.
Ebola virus disease evd, or simply ebola, is a viral haemorrhagic fever of humans and other primates caused by ebolaviruses. Ebola virus disease is one of the most deadly emerging infectious diseases in the world which causes. Relevant information was identified through a comprehensive literature search using. Current status of drug treatment against the disease caused. The 2014 ebola epidemic is the largest in history and is centered in the west african countries sierra leone, liberia, and guinea. Signs and symptoms typically start between two days and three weeks after contracting the virus with a fever, sore throat, muscular pain, and headaches. Download product insert pdfdownload safety data sheet sds pdf. The nih is helping guide two frontrunner ebola vaccine candidates through earlystage human trials and, barring safety or immunity problems, may have the vaccines ready for advanced testing in african and other volunteers as early as december, according to nih officials. The virus has no established origin, location, or habitat.
Fruit bats of the pteropodidae family are thought to be the natural host of ebola virus thought they themselves do not show any symptoms evd has a high mortality rate of up to 90%. The discovery is reported of a small molecule drug, gs5734, which has antiviral activity against ebola virus and other filoviruses, and is capable of providing postexposure therapeutic. Most important, as we confront an unprecedented recent studies have shown promise for a combination of ebola epidemic in west african countries that had previ monoclonal antibodies and for a small interfering rna ously not been affected and in an age when air travel brings compound bcx4430 as postexposure prophylaxis in us together like. Since 2014, the largest outbreak of ebola virus in recorded history spread into several adjacent west african nations.
Over the past 40 years, the virus has been linked to several high mortality outbreaks in africa with the recent west african outbreak resulting in over 11,000 deaths. Despite the unprecedented ebola virus outbreak response in west africa, no ebola medical countermeasures have been approved by the us food and drug administration. Ebola virus disease is a severe, often fatal, zoonotic infection caused by a virus of the filoviridae family genus ebolavirus. A broadspectrum antiviral small molecule is reported to act as an inhibitor of viral polymerase activity and is shown to be effective in protecting nonhuman primates from lethal filovirus. Pdf efficacy of galidesivir against ebola virus disease in rhesus. Communication resources communication resources ebola.
During 2014 another outbreak of ebola was reported from the democratic republic of congo. Some outbreaks in human history have proven the lethality. Clinical patterns, public health concerns is a concise description and discussion of the ebola virus and disease. In nonclinical studies involving lethal infections with ebola virus, marburg. Ebola virus ebov disease is an infectious condition with a high burden in global mortality and sequelae. Bcx4430 is an adenosine nucleoside analog with broadspectrum antiviral activity with ec 50 values ranging from 3. A molecule called bcx4430 rescued 17 of 18 monkeys after they were infected with the virus. In nonclinical studies involving lethal infections with ebola virus, marburg virus, rift valley fever virus, and yellow fever virus, bcx4430 has demonstrated pronounced efficacy. The adenosine nucleoside analog bcx4430 is a directacting antiviral drug under investigation for the treatment of serious and lifethreatening infections from highly pathogenic viruses, such as the ebola virus. Bcx4430 a broadspectrum antiviral adenosine nucleoside analog under development for the treatment of ebola virus disease. Sophie arie reports a few weeks ago, most people worldwide had probably never heard of ebola disease. We encourage developers to generate more information on the use of these medicines in the treatment of ebola patients.
The deadly and highly infectious ebola virus was discovered in 1976 in yambuku in the democratic republic of congo, 60 miles from the river after which it was named. Ev was first identified in 1976, the current one being the 25th known outbreak of ev infection. Ebola virus disease is a zoonosis caused by a virus of the family filoviridae. Bcx4430 is a novel adenosine analog that inhibits viral rna polymerase activity, which results in termination of rna synthesis.
Animal and human studies published in english were. Sep 12, 2015 in 2014 and 2015, the largest ebola virus disease evd outbreak in history affected large populations across west africa. Numerous therapeutics were explored or developed during the outbreak, including repurposed. For example, in the mouse bcx4430 has a 10 min halflife in plasma, but its tp in liver has a 4. The incubation period for ebola virus disease ranges from two to. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of bcx4430. The main lines of therapy are based on immunotherapy convalescent serum of patients and specific monoclonal antibodies, antiviral drugs favipiravir, bcx4430, brincidofovir, interfering rnas tkmebola and antisense oligonucleotides morpholino phosphorodiamidate and other drugs no antiviral clomiphene nsc62914, fgi103, amiloride and. Nih ebola response nih intramural research program.
Experimental ebola therapies thrust into spotlight jama. Bcx4430 inhibits ebola virus minigenome rna replication and hepatitis c virus. The response is now focused on intensive surveillance, including active case finding and investigation of suspected cases and alerts. Therapeutic efficacy of the small molecule gs5734 against. Pdf advancements in the therapy of ebola virus disease. Nih accelerates clinical trials of ebola vaccines fogarty. M against a panel of ebola, marburg, bunya, arena, paramyxo, corona and flaviviruses. Galidesivir bcx4430, immucillina is an antiviral drug, an adenosine analog a type of nucleoside analog.
The ebola outbreak in 2014 has killed many people in guinea, sierra leone, liberia and nigeria. Addressing therapeutic options for ebola virus infection in current. As the largest outbreak of ebola virus has forced hitherto neglected tropical diseases on to the public agenda, debate is growing over whether affected patients should have the chance to try experimental drugs. Potential and emerging treatment options for ebola virus. As efforts to successfully contain the largest outbreak of ebola virus disease in history prove elusive, the mounting number of cases and deaths has brought research to develop muchneeded treatments and protective vaccines into the spotlight. Bcx4430 is active in vitro against ebola virus and does not display any significant mutagen icity, as determined in an ames assay. To describe the current ebola virus epidemic and the potential options for treatment and prevention of ebola virus disease. A possible cure for ebola virus infection has been discovered. While ebola virus possesses the capacity to cause significant disease, humantohuman transmission has been viewed as limited because of the nonrespiratory mode of transmission requiring direct contact. Galidesivir bcx4430, immucillina is an antiviral drug, an adenosine analog it is developed.
Protection against filovirus diseases by a novel broad. The massive outbreak of ebola virus disease in west africa between 20 and 2016 resulted in intense efforts to evaluate the efficacy of several specific countermeasures developed through years of preclinical work, including the first clinical trials for therapeutics and vaccines. The intended audience is medical practitioners, including those working in endemic areas as well as healthfacility planners and public health practitioners. Global overview of ebola research european commission. A possible cure for ebola virus infection has been. Ebola virus, a member of the filoviridae family, is a causative agent of severe viral. Experimental ebola treatments still at early stage of. Alisporivir has limited antiviral effects against ebola virus. In nonclinical studies involving lethal infections with ebola virus, marburg virus, rift valley fever virus, and yellow fever virus, bcx4430 has. It is developed by biocryst pharmaceuticals with funding from niaid, originally intended as a treatment for hepatitis c, but subsequently developed as a potential treatment for deadly filovirus infections such as ebola virus disease and marburg virus disease.
Ebola virus disease evd is associated with haemorrhagic fever in humans and nonhuman primates, with a high rate of fatality up to 90%. The adenosine nucleoside analog bcx4430 is a directacting antiviral drug. Ebola virus disease is an infection of human and nonhuman primates with fatality rates of up to 90%. Bcx4430 has been demonstrated to protect against both ebola and marburg viruses. Bcx4430 a broadspectrum antiviral adenosine nucleoside. Clinical patterns, public health concerns joseph r. However, multiple valuable lessons have been learned about the conduct of clinical research in a resourcepoor, high riskpathogen setting. However, the effects of ribavirin in animal models of ebov infection have been modest, particularly in nonhuman primates, and although novel nucleoside analogs bcx4430 and gs5734 have shown efficacy against filoviruses in cynomolgus macaques 4, 5, a search for additional therapeutic candidates is warranted. Human to human transmission occurs through contact with body fluids from infected patients.
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