HIV-1 capsid protein (CA) (HIV-1 CA)

The HIV-1 capsid protein (CA) is a critical structural component of the Human Immunodeficiency Virus type 1, synthesized as part of the Gag polyprotein (UniProt: P04591). It assembles into a conical shell that protects the viral RNA genome and facilitates essential processes including reverse transcription and nuclear import (PubMed: 32814903). The monomer-monomer interface of CA contains a highly conserved hydrophobic pocket that serves as a binding site for host factors like CPSF6 and NUP153, which are necessary for viral trafficking and integration. Therapeutic targeting of this interface with small molecules, such as Lenacapavir, provides a multi-stage mechanism of action by interfering with capsid assembly, maturation, and uncoating (PubMed: 32690950). This target is particularly significant for the development of long-acting antiretroviral therapies due to the high potency and metabolic stability of capsid-binding compounds.

Other names

p24Gag-p24Capsid protein p24HIV-1 capsid protein monomer-monomer interfaceHIV-1 CA protein

Inhibition of HIV-1 replication by binding to the hydrophobic pocket at the interface between capsid protein (CA) monomers, which disrupts both the assembly of new viral capsids and the disassembly (uncoating) of the capsid in newly infected cells (PubMed: 32690950, FDA: Sunlenca).