This project will lead to early diagnosis of dengue fever so that treatment can occur much quicker for infected patients.
All computational models for the Dengue virus (DENV) NS1 protein, both in its monomeric and dimeric forms have been generated. From these models, researchers have identified druggable binding sites and the first round of in silico screening predicted a number of small molecules that will bind to these sites. The small molecules have been purchased and interaction with recombinant DENV NS1 protein will be tested using a variety of in vitro assays.
Dengue is the most prevalent mosquito-borne viral infection worldwide and is the leading cause of illness and death in tropical/subtropical areas (>390 million people are infected). There are no approved vaccines or drugs against the virus. While most infections resolve without medical intervention, a significant fraction of dengue patients develop hemorrhagic fever and shock syndrome, which if untreated can be fatal. Early supportive care is critical for management of the fever and maintaining the blood volume during hemorrhage. Because the initial symptoms of dengue are similar to many other mosquito transmitted viral infections, early and accurate diagnosis of the disease is critical for these patients.
Generally, current dengue virus assays are not sensitive enough, too expensive and/or time-consuming resulting in delayed/misguided medical intervention in up to 50% of cases. In developing countries, the ease of access, availability of required infrastructure and the cost of diagnosis are usually prohibitive. As such, the need for efficient low-cost diagnostic tools is urgent.
The viral glycoprotein NS1 is an ideal diagnostic marker because it can be detected in patient sera at the same time as symptoms develop. Unfortunately, current NS1-based assays vary greatly in their capacity to detect different dengue serotypes and secondary infections that can progress to hemorrhagic shock. To overcome these problems we will develop pan- and serotype-specific, high-affinity small molecules targeting the NS1 protein for accurate diagnosis of dengue infection. These small molecule ligands will be more stable, affordable and efficient for detecting dengue infection compared to current antibody-based diagnostic kits.
Dr. Tom Hobman, University of Alberta
Dr. Khaled Barakat, University of Alberta
Dr. Aloke Kumar, University of Alberta
Dr. Marawan Ahmed, University of Alberta
Dr. Easwaran Sreekumar, Rajiv Gandhi Centre for Biotechnology
Dr. Carlo Montemagno, University of Alberta
University of Alberta
Alberta Research Chemicals (ARC)
Alberta Virology Institute (AVI)
National Institute of Nanotechnology
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