ARCHIVED - Fighting the Threat of SARS
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November 05, 2005— Ottawa, Ontario
NRC researchers are working to improve our understanding and find ways to better combat infectious diseases such as Severe Acute Respiratory Syndrome (SARS). Although largely dormant at present, the world continues to live under the threat of another SARS outbreak. In the past year, two different NRC teams reported progress in the fight against SARS using vastly different approaches, one using the tools of biotechnology and the other using mathematics.
|NRC researcher working on mathematical modeling to better understand the precise extent to which isolation or quarantine is more effective against SARS.|
Using Math to fight SARS
Anyone who visited a hospital in the spring of 2003 will remember spending time in line waiting to be screened for SARS. If another outbreak were to occur, the same sorts of procedures would likely apply. In the continued absence of a vaccine or an effective rapid diagnosis tool, isolation (used for patients with symptoms of SARS) and quarantine (used for patients with an established link to the SARS virus) remain the best tools for limiting transmission of the virus.
NRC life sciences researchers in Winnipeg are part of a Canadian team that has applied the tools of mathematical modeling to better understand the precise extent to which isolation or quarantine is more effective. The goal of this research is to help public-health authorities make decisions in a situation where the health-care system is stretched thin, or a vaccine is not available.
By analyzing data collected during the outbreak, the team concluded that once the SARS outbreak began in Toronto, screening (used widely at points of entry into the country and at health-care facilities) had little impact on how fast the disease progressed. In contrast, simulations using the same data showed that the size and duration of an outbreak can be greatly influenced by the timely implementation of the isolation program. For example, if authorities had waited as few as five extra days in quarantining and isolating persons with probable cases of SARS, there would have been 16 additional deaths. Ultimately, researchers concluded that the isolation of individuals with symptoms of SARS, under stringent hygiene precautions, can lead to effective control in a community and may even eradicate the disease, provided there are no undetected new admissions of SARS-infected individuals.
NRC biotechnology researchers based in Montreal are also having an impact on SARS. Using computer prediction and modeling techniques, the team has built a model of the structure of a protein used by the SARS virus to help it reproduce, known as SARS PLpro. Proteins play an extremely important role in all organisms. Generally speaking, proteins are responsible for carrying out all of the functions necessary for the organism to live.
While identifying proteins is the first step, understanding their physical structure is key to learning more about their function, a task which the team accomplished using computer modeling techniques. The team was able to translate extensive expertise with another related group of proteins, the cysteine proteases, and use this to help in identifying a new and unexpected function for the SARS PLpro. The model revealed that the viral protease might mimic the function of enzymes present in the human host, known as deubiquitinating enzymes. This prediction was later confirmed by the NRC researchers.
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Ubiquitination is an important process that helps regulate several key cellular functions. The process, the subject of the 2004 Nobel Prize in Chemistry, involves the addition of a protein called ubiquitin which, when present, sends a message that the ubiquitinated protein has finished its work and needs to be eliminated or "degraded". NRC's model suggests that the SARS PLpro enzyme, in addition to helping the virus replicate, can also reverse the ubiquitination process. The finding has raised important questions about whether this ability to deubiquitinate proteins and, therefore, interfere with important cellular functions could help explain why the SARS virus is so effective in evading cellular defenses. This discovery could lead to new strategies for developing anti-viral drugs against SARS and other related viruses.
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