The primary mission of Core E of the Antiviral Countermeasures Development Center (AC/DC) is to determine X-ray or cryo-EM structures of lead compounds identified by the Research Projects in complex with their viral protein targets. The resulting atomic-level information will be used to rationally design or optimize lead compounds in silico, as well as determine molecular mechanisms of action. Core E will also provide protein expression and purification support to Research Projects that need highly active and pure proteins for compound validation or novel screening approaches. Additionally, Core E will perform biophysical binding studies to determine thermodynamic and kinetic binding constants for lead compounds via isothermal titration calorimetry and surface plasmon resonance. These techniques can be used to identify candidates that bind directly to the target protein as well as enable compound optimization aimed at improving specific binding parameters. Collectively, the services provided by Core E will accelerate the development of orally bioavailable antivirals against SARS-CoV-2 and other RNA viruses with pandemic potential as well as provide novel insights into the structure, function, and inhibition of important viral proteins.
