Trends in Molecular Medicine
ReviewClinical Evaluation of Ebola Virus Disease Therapeutics
Section snippets
EVD Therapeutics Are Urgently Needed
The outbreak of Ebola virus (EBOV) in West Africa from December 2013 to March 2016 was the largest ever reported to date, with 28 616 cases and 11 310 deaths (http://apps.who.int/iris/bitstream/10665/208883/1/ebolasitrep_10Jun2016_eng.pdf?ua=1). EBOV belongs to the genus Ebolavirus, which causes EVD – clinically manifested by a spectrum of symptoms including fever, fatigue, muscle pain, vomiting, diarrhea, anorexia, rash, bleeding, and multiorgan failure 1, 2. Disease fatality rate can be up to
Small Molecule Inhibitors: Direct Intracellular Inhibition of EBOV
A popular approach in the search for effective therapeutics is the identification and characterization of small molecules that might inhibit EBOV; presumably through different mechanisms, including suppression of viral transcription and replication. Many small molecules, such as brincidofovir, BCX4430, favipiravir, GS-5734, and AVI-6002, have been shown to be protective in cultured cells, or in animal models such as mice and NHPs 15, 16, but remain to be assessed against EVD in humans.
IFN-β, a Proof-of-Concept Immunomodulation Trial
IFNs are important components of innate immunity against viral infection and have been used as broad-spectrum antiviral therapies. Protective effects of IFN-α, -β, or -γ against EBOV have been tested in different animal models including mice 49, 50, guinea pigs [51], and NHPs 52, 53. In one EVD patient, IFNs prepared from Sendai-virus-stimulated peripheral lymphocytes were administered intramuscularly in combination with convalescent serum, and this patient survived [54]. However, IFN
Concluding Remarks
Despite challenges of testing candidate therapeutics in the midst of EVD outbreaks, valuable experience has been gained in the design and conduct of expedited clinical trials. A common problem with the trials discussed here has been the relatively low enrollment of patients because trials may have been initiated late during an outbreak, rendering it difficult to conclude whether a specific treatment protocol presented any statistically significant benefits to patients. Nonrandomized single-arm
Acknowledgments
This study was supported by the Public Health Agency of Canada, and partially supported by a NIH grant (U19 AI109762-1) to Gary Kobinger and Xiangguo Qiu, and the National Science and Technology Major Project (2016ZX10004222) to George F. Gao, Yuhai Bi and Gary Wong. The authors have no conflicts of interest to declare. Gary Wong, Gary Kobinger, and Xiangguo Qiu were involved in the development and characterization of ZMapp discussed in this review. Yuhai Bi is supported by the Youth Innovation
Glossary
- Convalescent serum/plasma
- collected from convalescent patients who presumably carry specific antibodies against the pathogen causing the disease. Convalescent plasma, serum, or whole blood can be used as therapies for infectious diseases, particularly under circumstances of limited medical resources.
- Cycle threshold (Ct)
- in real-time quantitative PCR reaction, Ct refers to the cycle at which fluorescent signals from PCR amplification exceed background signals. It is a measurement of the amount of
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2019, Biosafety and HealthCitation Excerpt :Ebola virus (EBOV) is a lethal human pathogen that causes a type of haemorrhagic fever with a high fatality rate [2–4]. EBOV infection causes Ebola virus disease (EVD), which has become global concerns since EVD outbreak in 2014 and then has remained as the largest occurrence of viral infection [1–4]. Unfortunately, no antiviral medications are available so far for EVD treatment [5,6].
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