Lenacapavir (Sunlenca): A Long‐acting HIV ‐1 Capsid Protein Inhibitor for Treating HIV Infection

At the end of 2022, the FDA approved Gilead's long-acting human immunodeficiency virus-1 (HIV-1) drug lenacapavir (Sunlenca), a first-in-class HIV capsid protein inhibitor, providing a new treatment option for people suffering from multidrug resistance. Long-acting HIV-1 antiretroviral therapy, characterized by a greater than 1-month dosing interval, offers significant advantages over daily oral therapy. The capsid core of HIV-1 is a large macromolecular assembly that surrounds the viral genome and is an essential component of the infectious virus. The interactions between capsid proteins are the key determinants for the stability of the mature capsid, which is essential for the precise timing of the assembly and uncoating steps in the HIV-1 life cycle. Creating small molecules that either stabilize or destabilize the capsid core is a promising strategy for the discovery of novel antiviral treatments.