Lenacapavir-induced Lattice Hyperstabilization is Central to HIV-1 Capsid Failure at the Nuclear Pore Complex and in the Cytoplasm

Lenacapavir (LEN) is the first HIV-1 capsid inhibitor approved for clinical use. It inhibits multiple steps of the viral life cycle; however, the molecular details of the effect of LEN on capsid structure and the mechanistic steps of the inhibition are not understood. Recent studies show that intact cone-shaped capsids and capsids with LEN-induced breaks can dock at nuclear pore complexes (NPC), but only intact capsids enter the nucleus. In this work, we combined large-scale coarse-grained molec