Product Development: Drugs
Research Project 1: Dominique Missiakas, Andrzej Joachimiak, Olaf Schneewind and colleagues identified sortizins (small molecules isolated after a screen of 135,000 NSRB compounds) that inhibit sortase enzymes. Sortases function as transpeptidase and anchor surface proteins to the cell wall envelope of Gram-positive bacteria. Sortases are viewed as targets of antiinfective therapy for B. anthracis and drug-resistant S. aureus, S. pneumoniae, S. epidermidis, E. faecalis. The key question is whether sortizin-mediated inhibition is therapeutic in animal models of anthrax disease.Research Project 2: Joseph Barbieri, Dan Rich and colleagues identified BABIM analog compounds as inhibitors of botulinum neurotoxins. The key question is to identify BABIM compounds that can inhibit all neurotoxins, and whether this inhibition can be therapeutic in animal models of botulism disease.
Research Project 6: Richard Kuhn, Michael Rossman, Mark Cushman, Carol Post and Janet Smith report on the identification of compounds that inhibit class II fusion proteins of flaviviruses and alphaviruses as well as compounds that interfere with alphavirus capsid protein function. The key question is whether these compounds display therapeutic value in tissue culture or animal models of disease.