Computational Modeling of IN-CTD/TAR Complex to Elucidate Additional Strategies to Inhibit HIV-1 Replication

Quinolinonyl Derivatives as Dual Inhibitors of the HIV-1 Integrase Catalytic Site and Integrase–RNA interactions

“…IN exhibits distinct preference for select gRNA structural elements such as trans-activation response (TAR) RNA. IN CTD plays the crucial role in binding the gRNA. − ALLINIs impair IN–gRNA interactions by inducing aberrant IN multimerization, which results in the formation of eccentric particles, where vRNPs are mislocalized outside of the mature capsid. ,,, The IN tetramers have a strikingly higher affinity toward gRNA than IN monomers or dimers and, consequently, interfering with proper IN tetramerization inhibits the IN binding to gRNA …”