Methods of identifying a compound that inhibit, enhance and/or misdirect
assembly of a viral capsid include providing fluorescently-labeled capsid
polypeptides labeled with a fluorescent dye that changes fluorescence at
high concentration, wherein assembly of the capsid polypeptides into the
viral capsid results in juxtaposition of at least one of the N-terminus
and C-terminus of the capsid polypeptides. In vitro assembly reactions
are performed utilizing the labeled capsid polypeptide in the presence of
the at least one test compound, and an amount of fluorescence is detected
at at least one time point following induction of assembly, wherein the
induction of assembly is detected as a change in the fluorescence of the
sample. It is then determined whether the change in fluorescence detected
in the presence of the at least one test compound following induction of
assembly is decreased, increased, or occurs at a fast rate when compared
to the fluorescence detected in the absence of the at least one test
compound, wherein such decrease is an indication that the at least one
test compound interferes with assembly of the viral capsid.