Articles of Significant Interest in This Issue

Abstract

An Antiretroviral Small Molecule That Appears To Inhibit HIV-1 Assembly by Targeting the Host Most antiretroviral drugs target viral proteins, thereby selecting for drug-resistant HIV-1 strains that undermine use of such drugs for HIV-1 treatment and prevention. Overcoming this problem requires novel drugs less prone to selecting resistant virus, such as host-targeting drugs. Reed et al. (e00883-20) used cell-free systems that recapitulate host-catalyzed viral capsid assembly pathways to identify small molecules that inhibit HIV-1 replication in T cells with nanomolar efficacy by blocking immature capsid assembly. These compounds colocalize with HIV-1 Gag and host enzymes found in HIV-1 assembly intermediates but do not select for viral resistance mutations, consistent with a host-targeting mechanism of action.