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New insights into HIV-1 capsid disruption Open doors for novel therapies
Announcing a new publication for Acta Materia Medica magazine. The HIV-1 capsid protein (CA) plays a critical role in viral replication by orchestrating nuclear entry through interactions with host nuclear pore complexes (NPCs). Recent studies have shown that HIV-1 CA actively disrupts NPC architecture via phenylalanine-glycine (FG) repeat nucleoporin interactions, thereby allowing nuclear translocation of viral components. This mechanistic insight drove the development of lenacapavir, the first CA inhibitor approved for multidrug-resistant HIV-1. Lenacapavir competitively blocks Ca-NPC binding, stabilizes cytoplasmic capsids, disrupts viral maturation, and exhibits pan-stage antiviral efficacy and long-acting pharmacokinetics. Clinical studies have shown...
New insights into HIV-1 capsid disruption Open doors for novel therapies
Announcing a new release forActa Materia MedicaMagazine. The HIV-1 capsid protein (CA) plays a critical role in viral replication by orchestrating nuclear entry through interactions with host nuclear pore complexes (NPCs).
Recent studies have shown that HIV-1 CA actively disrupts NPC architecture via phenylalanine-glycine (FG) repeat nucleoporin interactions, thereby allowing nuclear translocation of viral components. This mechanistic insight drove the development of lenacapavir, the first CA inhibitor approved for multidrug-resistant HIV-1.
Lenacapavir competitively blocks Ca-NPC binding, stabilizes cytoplasmic capsids, disrupts viral maturation, and exhibits pan-stage antiviral efficacy and long-acting pharmacokinetics. Clinical trials have demonstrated 100% prophylactic efficacy and the potential to reduce global HIV incidence. Advances in structural biology, molecular dynamics simulations, and nanotechnology are expected to further influence next-generation therapeutic strategies targeting CA-host interactions.
These results not only redefine HIV-1 treatment paradigms but also have broader implications for combating CA-dependent viruses.
Sources:
Wang, M.,et al.(2025) Revolutionizing HIV treatment: unveiling the new frontiers of HIV capsid research. Acta Materia Medica. doi.org/10.15212/AMM-2025-0012.