Phase diagrams map the properties of antiviral agents directed against hepatitis B virus core assembly

Assembly effectors are small molecules that induce inappropriate virus capsid assembly to antiviral effect. To identify attributes of hepatitis B virus (HBV) assembly effectors, assembly reaction products (normal capsid, noncapsid polymer, intermediates, and free dimeric core protein) were quantified in the presence of three experimental effectors: HAP12, HAP13, and AT-130. Ef-fectors bound stoichiometrically to capsid protein polymers, but not free protein. Thermodynamic and kinetic effects, not aber-rant assembly, correlate with maximal antiviral activity. Hepatitis B virus (HBV) is a global public health problem. Ac-cording toWorldHealthOrganization estimates, 360million people suffer from chronic HBV infection, contributing to ap-proximately 600,000 deaths every year (1). HBV-specific antiviral drug development has focused on targeting the viral reverse trans-criptase (RT). However, RT inhibitors do not usually clear HBV infection, even after prolonged treatment (2–4). Furthermore, cessation of RT inhibitors can lead to life-threatening viral flares; therefore, they are generally a lifelong therapy (5). An alternative therapeutic target is highly desirable. One attractive target is as-sembly of HBV’s capsid from core protein