The focus of my research is to study how viruses replicate and cause disease. One major area of our research is to investigate the replication of coronaviruses, including the recently emerged coronavirus that causes Severe Acute Respiratory Syndrome (SARS-CoV). We study the expression, proteolytic processing and function of the coronavirus RNA polymerase polyprotein. This complex polyprotein holds the key to understanding how coronavirus replication is regulated. We found that the polyprotein is processed into 16 products by viral proteases. Viral proteases are attractive targets for antiviral drug development. Our current efforts are aimed at developing and testing protease inhibitors for their ability to inhibit coronavirus replication, and determining if viral proteases process host cell proteins to modulate the cellular environment and facilitate viral replication.
We also study the etiology and pathogenesis of Kawasaki Disease (KD). KD is the leading cause of acquired heart disease in children in developed nations, but the cause of KD is unknown. Using KD-specific antibodies, we showed that an antigen is found in both the coronary arteries and in bronchial epithelial cells of KD patients, suggesting a respiratory portal of entry for the KD agent. We are currently using human airway epithelial cell cultures to identify and propagate microbes associated with KD.