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Coronavirus Biology and Pathogenesis
On the Front Lines
Approaches to Vaccines and Drug Development
Blocking SARS Virus Fusion
Lessons in Interventions for SARS
Status of Drug Screening vs. SARS
Adenovirus Vector Technologies for Vaccines
Some Approaches to Vaccine Development
Panel 3 Discussion
Future Perspectives on Emerging Infections
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SARS in the Context of Emerging Infectious Threats SARS in the Context of Emerging Infectious Threats
Approaches to Vaccines and Drug Development
Blocking SARS Virus Fusion

David Ho, Aaron Diamond AIDS Research Center, New York
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Highlights

Visit to China
• The concern among people and the socioeconomic impact are high in China.
• China recognizes that it missed opportunities to address SARS more effectively and is now galvanized against it.
• Efforts include sequencing to enable molecular epidemiological testing, vaccine research, searching for an animal source, and building BL3 and BL4 labs.

S Gene Structure Resembles HIV gp 41
• Spike protein has two regions of alpha-helical structure with heptad repeats, like gp41 and other envelope virus structural proteins.
• Binding of gp120 to target host cells results in conformational changes that result in a hairpin formation, close approximation of viral and host membrane, and fusion.
• Peptides derived from repeat regions can inhibit virus entry and replication of HIV and other viruses; T-20, or Fuzeon, has recently been licensed as a drug.
• Evidence suggests that peptides lock the virus into an intermediate conformation, preventing fusion.

Testing peptides against SARS Coronavirus
• A qualitative CPE assay and a plaque assay in Vero cells have been used to test twelve peptides; five showed varying degrees of antiviral activity.
• Peptide therapeutics are difficult to make and are likely to be injectible rather than oral pills; development is rapid and they are generally not very toxic.
• Activity may be improved upon by optimizing the peptide sequence used.

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