Bevirimat - Mechanism of Action

Mechanism of Action

Like protease inhibitors, bevirimat and other maturation inhibitors interfere with protease processing of newly translated HIV polyprotein precursor, called gag. Gag is an essential structural protein of the HIV virus. Gag undergoes a chain of interactions both with itself and with other cellular and viral factors to accomplish the assembly of infectious virus particles. HIV assembly is a two-stage process involving an intermediate immature capsid that undergoes a structurally dramatic maturation to yield the infectious particle. This alteration is mediated by the viral protease, which cleaves the Gag polyprotein precursor, allowing the freed parts to reassemble to form the core of the mature virus particle. Bevirimat prevents this viral replication by specifically inhibiting cleavage of the capsid protein (CA) from the SP1 spacer protein. First, bevirimat enters a growing virus particle as it buds from an infected cell and binds to the Gag polypeptide at the CA/SP1 cleavage site. This prevents the protease enzyme from cleaving CA-SP1. As the capsid protein remains bound to SP1, the virus particle core is prevented from compressing into its normal mature shape, which is crucial for infectivity, resulting in the release of an immature, non-infectious particle.