New Orleans -- Dr. William Gallaher, Professor of Microbiology, Immunology, and Parasitology at Louisiana State University (LSU) Health Sciences Center in New Orleans, with collaboration from Dr. Robert Garry, Professor of Microbiology and Immunology at Tulane University Health Sciences Center, has developed a model of a critical surface protein of the virus that causes Severe Acute Respiratory Syndrome (SARS) that could pave the way for new effective antiviral drugs to treat it.
Dr. Gallaher, who previously discovered how both the Ebola (1996) and Human Immunodeficiency Viruses (1988) invade cells, and Dr. Garry have arranged for the model to be posted on the website, All of Virology on the WWW, www.virology.net so that scientists around the world working on SARS will have immediate and full access to it.
As a result of worldwide collaboration among hospitals, laboratories, universities and public health officials, the causative agent of SARS has been recently identified as a new strain of human virus in the family of coronaviruses. The protein on the surface of the virus, called the spike glycoprotein, has been identified as the protein responsible for entry of the virus into susceptible cells. Certain regions of this protein have previously been identified as particularly critical to the process of fusion that melds the viral membrane to the cell membrane.
Prior to the SARS outbreak, Drs. Gallaher and Garry began a research project to integrate what was known of the coronavirus spike protein into a model of its overall structure. When the genetic sequence of the SARS coronavirus was announced, they were uniquely positioned to analyze that sequence and develop a model that covers the last 314 amino acids of the spike glycoprotein just before the protein is anchored into the viral envelope. This portion has a high propensity to form a pair of helical fibers that comprise the stalk of the lollipop-like structure of the viral surface spikes.
"Despite a great deal of diversity in their molecular structure, the fusion glycoproteins of the viruses causing SARS, HIV and Ebola are all kissing cousins from the point of view of overall structure and function," said Dr. Gallaher, "so we know quite a bit about the SARS coronavirus. We are designing drugs, such as peptide analogues or peptidomimetics of this structure, that are predicted to have significant antiviral activity." (Peptidomimetics are small molecules that mimic the key features, but are more stable, more easily formulated as well as cheaper and easier to produce than peptides.)
"Our studies over the past twenty years have put us in the position to design predicted inhibitors of the SARS coronavirus in a short time frame," said Dr. Garry.
The research team is currently investigating and testing such peptides as antiviral fusion inhibitors against coronaviruses in a manner that does not pose a biohazard to human beings. They are also investigating and testing current reagents such as human monoclonal antibodies as well as already licensed antiviral drugs that may have efficacy against SARS.
Materials provided by Louisiana State University Health Science Center. Note: Content may be edited for style and length.
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