Our study, however, indicates that interaction of CD4-primed virus with a CCR5-mimetic may irreversibly strip the virus of its ability to infect cells by catalyzing the transition of Env into a thermodynamically stable, activated state, suggesting that the improved performance of CD4-CCR5 fusion mimetics in inhibiting HIV-1 infection may stem from their ability to irreversibly inactivate the virus. Here, CD4 is linked to HIV-1 infection.