Grant: Operating Grant

Viral diseases continue to be a major cause of disease despite the successful development of many vaccines and 45 antiviral drugs. No vaccines exist against important viruses such as hepatitis C virus, for example. No fully protective vaccines exist against others such as influenza (flu). No treatments exist to cure some chronic viral infections either, such as hepatitis B or herpesvirus. Some viruses such as influenza are extremely variable, which makes it difficult to target them with vaccines or antiviral drugs. Viruses new to the human population continuously emerge, such as SARS and the new SARS-like coronavirus in the UK and the Arabic peninsula. There is even the possibility of the intentional release of very virulent viruses as biological or terrorist weapons. In brief, viral diseases are a continuous threat to human health, and result in a heavy burden to the Canadian health care system and its resources. Viruses have a greater impact on certain marginalized populations. Women, the elderly and the very young are particularly susceptible to viral diseases. We use small chemicals as probes to explore virus functions that are essential for the virus to gain entry into a cell, to reproduce itself within a cell, and to cause disease. A major advantage of our approach is that it provides information and lead compounds for developing novel antiviral drugs. These lead compounds often have several advantages over conventional antivirals. They tend to be effective against several viruses, and they minimize the selection for viral resistance. In the research proposed here, we will continue our studies that have already uncovered a novel family of antivirals, the RAFIs. These antivirals are active against a variety of viruses, including influenza, hepatitis C and herpesviruses. Our proposed studies will result in a better understanding of how viruses enter cells. This new knowledge, in turn, can be used to the development of better antivirals.