Basic Science to Design Better Drugs (Darst, Campbell)

Structural biologists Seth Darst and Elizabeth Campbell are experts in determining the structure of RNA polymerase complexes bound to the templates that they copy. The SARS-CoV-2 RNA polymerase is essential for viral replication and a prime target for drug treatment. By understanding in atomic-level detail how existing inhibitors bind and inhibit the enzyme, they can identify ways to modify current inhibitors to make them specifically effective against SARSCoV- 2. In collaboration with biochemist Brian Chait, they will also identify all the proteins comprising the RNA replication complex in living cells. This will likely include proteins made both by the virus and by host cells, which may identify new therapeutic targets. They plan to determine the atomic-level structure of the complex by cryo-electron microscopy. Seth Darst seth.darst@rockefeller.edu 212-327-8000