Suppression of HIV-1 replication via inhibition of human flap endonuclease-1-mediated HIV-1 central DNA flap processing

摘要

FEN-1 is involved in processing HIV central DNA flap (CDF) and is a target for intervention of HIV-1 replication. Inhibition of HIV-1 CDF removal by expression of D181A FEN-1 mutant suppresses viral DNA replication, further demonstrating that FEN-1 is a target. Methods of identifying and using molecules that inhibit FEN-1 processing HIV-1 CDF and other methods of inhibiting FEN-1 processing are provided. Useful small molecules specifically suppress FEN-1 cleavage of HIV CDF but have little effect on FEN-1's function in RNA-DNA primer removal. Pentamidine inhibits HIV replication by suppressing FEN-1-mediated HIV-CDF processing.