HIV capsid

Class

Capsid inhibitor

The HIV capsid is the conical protein shell, built from repeating copies of the capsid protein (CA, also called p24), that encases the virus’s RNA genome and the enzymes needed for early infection steps. After the virus enters a cell, this shell must disassemble in a precisely timed process called uncoating, and later in the viral life cycle, capsid protein must reassemble correctly during particle maturation to produce infectious new virions. Because the capsid participates in both an early stage (protecting the genome, enabling trafficking to the nucleus) and a late stage (correct assembly of new particles), interfering with its structure can block the virus at multiple points rather than just one. This is the rationale behind capsid inhibitors: small molecules designed to bind the capsid lattice and either destabilize it prematurely or lock it into a nonfunctional form. The mechanism matters most in chronic HIV infection, particularly for individuals whose virus has developed resistance to other antiretroviral drug classes, since a distinct target with a different resistance profile can be combined with existing regimens. It also has been explored with modalities beyond small molecules, reflecting broader efforts to attack this structural target from more than one angle.