Ebola research projects at the National Microbiology Laboratory
1 Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry. Zheng W, Yang S, Xu M, Lee E, Gorshkov K, Shiryaev S, He S*, Sun W, Cheng Y-S, Hu X, Tharappel A, Lu B, Pinto A, Farhy C, Huang C-T, Zhang Z*, Zhu W*, Wu Y, Zhou Y, Song G, Zhu H, Shamim K, Martínez-Romero C, Garcia-Sastre A, Preston R, Jayaweera D, Huang R, Huang W, Xia M, Simeonov A, Ming G, Qiu X*, Terskikh A, Tang H, and Song H. Cell Discov 2018 Jun 5; 4:31. doi: https://doi.org/10.1038/s41421-018-0034-1
2 Ebola virus requires phosphatidylinositol (3,5) bisphosphate production for efficient viral entry. Qiu S, Leung A*, Bo Y, Kozak RA, Anand SP, Warkentin C, Salambanga FDR, Cui J, Kobinger G, Kobasa D*, Côté M. Virology 2018 Jan 1; 513:17-28. doi: https://doi.org/10.1016/j.virol.2017.09.028
3 Delivering Prolonged Intensive Care to a Non-human Primate: A High Fidelity Animal Model of Critical Illness. Poliquin PG*, Biondi M, Ranadheera C*, Hagan M*, Bello A*, Racine T, Allan M*, Funk D*, Hansen G, Hancock BJ, Kesselman M, Mortimer T, Kumar A, Jones S, Leung A*, Grolla A*, Tran KN*, Tierney K*, Qiu X*, Kobasa D*, Strong JE*. Sci Rep 2017 Apr 26; 7(1):1204. doi: https://doi.org/10.1038/s41598-017-01107-6
Through partnerships with Global Affairs Canada and collaborations with individual African countries, the NML supports a number of efforts to address Ebola outbreaks in Africa. Further, the NML has an established leadership role in international Ebola outbreak emergency response and domestic diagnostic support. This science story provides a glimpse into some of NML’s work, specifically with respect to the Ebola research projects funded to 2021.
What was known about this area prior to your work, and why was the research done?
The NML has and continues to play a significant role in shaping how Ebola virus disease (EVD) is treated. Collaboratively, the NML developed the Ebola vaccine (VSV-Ebola) and antibody therapy (ZMapp), both currently used in Ebola outbreak management globally. The NML continues to be a key national and international leader in the fight against Ebola virus (EBOV). In recognition of our key leadership role, the NML received funding to conduct Ebola specific research projects. These projects focus on three areas: 1) applied diagnostics; 2) medical countermeasures; and 3) building national capacity for high consequence pathogens. Collectively, these Ebola research projects will help Canada and the global community further anticipate, prepare for and respond to public health threats related to EBOV.
What are your most significant findings and the implications or impact of this research?
The following describes the initial findings of the Ebola research projects to date, broken into the three main areas of research.
1) Applied Diagnostics
This group of projects focus on the NML’s diagnostic approaches for EBOV. One project focuses on updating and enhancing NML’s mobile laboratory by increasing the number of accredited tests for EBOV, and by developing a quality management system for standard operating procedures. Another project looks at augmenting our diagnostic assays for the field with rapid detection tests and using next generation sequencing. In doing so, this will allow the NML to obtain full genome sequences for further study, assist in epidemiological studies and detection of new isolates in an outbreak setting. Our third project, in collaboration with the NML’s National HIV and Retrovirology Laboratories, is to build an early warning system for detection of EBOV in Africa. Implementation of an early warning system for detection of EBOV in Africa is an important step in preventing large-scale outbreaks from occurring and/or spreading.
2) Medical Countermeasures for Ebola Virus
As the NML works to investigate alternate medical countermeasures to EBOV, our research and findings in this area has the potential to shape future response to and treatment of EVD. In one study, we discovered that certain small molecules have the ability to inhibit Ebola virus infection (in vitro and in vivo), and that these molecules show potent inhibition against EBOV when tested in mice in vitro1. In a second study, we also found that some small molecules can inhibit the ability of EBOV to infect cells by blocking the production of key host cell membrane components and interaction with membrane proteins2. By identifying small molecules that could effectively inhibit EBOV, treatment options against EBOV could potentially to be broadened, thereby leading to the development of alternate medical countermeasures.
3) Building National Capacity for High Consequence Pathogens
To understand if supportive care can help improve patient outcomes of fulminant EVD, this group of studies included the development of a non-human primate intensive care unit (NHP-ICU) in collaboration with health care partners. In the NHP-ICU, EVD was studied under high containment conditions. In our studies, we demonstrated that while supportive care did not improve patient outcomes, it did show the need for complex training, equipment, materials, safety considerations and human resources3 that are required to manage patients with high consequence pathogens. These studies can be used to support cross training of local hospital staff and developing standards and procedures for managing patients infected with high consequence pathogens, including EBOV. Our data collected from the NHP-ICU can be used to inform decisions made in Canadian hospitals related to treatment of EVD patients, allowing for proper patient management, prevention of transmission and ultimately enhancing Canadian public health security.
The current Ebola outbreak in the Democratic Republic of Congo and lessons learned from the West Africa Ebola outbreak provide strong examples of the need to be well prepared to handle potential Ebola cases imported into Canada. Ultimately, this work collectively serves to protect Canadians and global citizens, and can prevent outbreak spread. These findings can also help guide patient care in Canada and assist global emergency preparedness worldwide.
Additional References of Significance:
- Wong G, He S*, Leung A*, Cao W*, Bi Y, Zhang Z*, Zhu W*, Wang L, Zhao Y, Cheng K*, Liu D, Liu W, Kobasa D*, Gao GF, Qiu X*. Naturally occurring single mutations in Ebola virus observably impact infectivity. J Virol 2018 Dec 10; 93(1) e01098-18. doi: https://doi.org/10.1128/JVI.01098-18
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