Design and Testing of novel compounds effective against SARS-CoV-2
Sidorenko, Hashimoto, Moriya, Johnson
We have assembled a consortium of biomedical scientist to explore the potential of antiviral agents known to be effective against a broad range of RNA viruses, including coronaviruses. In so doing, we build on Grollman’s and Johnson’s earlier research on aurintricarboxylic acid (ATA) and emetine, including studies that support a selective mechanism(s) for their antiviral activity. Our experienced multidisciplinary team is composed of SBU laboratories headed by Grollman, Johnson and Garcia-Diaz; the Breslauer laboratory at Rutger University, and the Peden laboratory of DNA viruses at the FDA.
Our pilot studies were initiated in March 2020. We have made excellent progress to date, and results of pilot studies will be published in the near future.
The LCB will establish experimental systems designed to explore, at the molecular and cellular level, the mechanism(s) of action of our several lead compounds. This mechanistic info will provide clues to the structural features involved in selective toxicity and specificity of candidate inhibitors.
Medicinal chemists have looked forward to the day when rational drug design could incorporate the three-dimensional structure of the relevant receptor. We utilize this approach in our program, with Garcia-Diaz performing structural studies, using facilities in Brookhaven National Laboratories.
Crystallographic structures of RdRp and 40s ribosomes are available, facilitating interpretation of the high-resolution structure of these complex macromolecules when bound to our lead compounds and their derivatives. Based on this info, structures of lead compounds will be modified to achieve optimal therapeutic effects.