Pyrazolo-Piperidines Exhibit Dual Inhibition of CCR5/CXCR4 HIV Entry and Reverse Transcriptase

We report novel anti-HIV-1 agents with combined dual host–pathogen pharmacology. Lead compound 3, composed of a pyrazole-piperidine core, exhibits three concurrent mechanisms of action: (1) non-nucleoside reverse transcriptase inhibition, (2) CCR5-mediated M-tropic viral entry inhibition, and (3) CXCR4-based T-tropic viral entry inhibition that maintains native chemokine ligand binding. This discovery identifies important tool compounds for studying viral infectivity and prototype agents that block HIV-1 entry through dual chemokine receptor ligation.