lenacapavir a HIV-1 capsid inhibitor

Last edited 12/2022 and last reviewed 01/2023

Lenacapavir a HIV-1 capsid inhibitor

• is the first of a new class of drug called capsid inhibitors to be FDA-approved for treating HIV-1
• is a novel, first-in-class, multistage, selective inhibitor of HIV capsid protein
• blocks the HIV-1 virus' protein shell and interferes with essential steps of the virus' evolution
  
• binds to the HIV-1 capsid to potently inhibits HIV-1 replication in vitro and in vivo (1)
  • in clinical studies, lenacapavir has demonstrated successful antiviral activity and adequate pharmacokinetic exposure for up to 6 months after a single subcutaneous injection (2)
  • by binding to two neighbouring subunits of the HIV capsid protein, lenacapavir interferes with their interactions essential for multiple phases of the viral replication cycle (1,2) and include:
    • capsid-mediated nuclear uptake of preintegration complexes,
    • virion production and proper capsid core formation
    • virus produced in the presence of lenacapavir displays improperly shaped capsids that can enter new target cells but cannot replicate
      

Reference:

• Selyutina A, Hu P, Miller S, Simons LM, Yu HJ, Hultquist JF, Lee K, KewalRamani VN, Diaz-Griffero F. GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors. iScience. 2021 Dec 9;25(1):103593
• Dvory-Sobol H, Shaik N, Callebaut C, Rhee MS. Lenacapavir: a first-in-class HIV-1 capsid inhibitor. Curr Opin HIV AIDS. 2022 Jan 1;17(1):15-21.