Project Grant R21AI198995

The National Institute of Allergy and Infectious Diseases awarded $232,737 to the Trustees of Indiana University on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to redesign hepatitis B virus capsid assembly modulators that induce apoptosis in infected cells.

The research addresses the absence of a cure for chronic HBV despite available reverse transcriptase inhibitor treatments that control but do not eliminate the virus. The project targets the viral capsid protein, which plays a critical role throughout the HBV replication cycle—from packaging viral RNA to intracellular trafficking and maintaining infection. The recipient will develop improved capsid assembly modulators (CAMs) that accelerate abnormal assembly, preventing formation of infectious particles and accumulating capsid complexes in the nucleus of infected cells to trigger apoptosis. The hypothesis is that clearing infected hepatocytes through apoptosis could allow replacement with healthy newly divided cells, potentially establishing a functional cure. Current apoptosis-driving CAMs are slow-acting and require high intracellular concentrations; the project applies structure-guided medicinal chemistry approaches to design modulators with improved potency and kinetics.

Performance occurs in Bloomington, Indiana, with period of performance from September 1, 2026 through August 31, 2028. The award is classified as a Project Grant under the assistance type.