A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly.

ABSTRACT: Heteroaryldihydropyrimidines (HAPs) are a new class of antivirals inhibiting production of hepatitis B virus (HBV) virions in tissue culture. Here, we examine the effect of a representative HAP molecule, methyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(pyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate (HAP-1), on the in vitro assembly of HBV capsid protein (Cp). HAP-1 enhances the rate and extent of Cp assembly over a broad concentration range. Aberrant particles, dominated by hexagonal arrays of Cp, were observed from assembly reactions with high HAP-1 concentrations. HAP-1 also led to dissociation of metastable HBV capsids, overcoming a kinetic barrier to dissociation by scavenging Cp and redirecting its assembly into hexamer-rich structures. Thus, HAP drugs act as allosteric effectors tha

SUBMITTER: Stray SJ 

PROVIDER: S-EPMC1149411 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature