Abstract: The CAI-binding pocket in HIV-1 CA CTD can be used as target for antiviral development. In the present study, 399 compounds were screened against CA CTD-CAI interaction by a homogeneous time-resolved fluorescence (HTRF) assay. A compound, ciclesonide, was identified as inhibitor by competing with CAI binding to CA CTD (IC50=6.06 μmol/L). Biolayer interferometry assay demonstrated that ciclesonide preferentially binded to CA hexamer (KD=159 nmol/L) other than monomer (KD=1.68 mmol/L). In the CA assembly assay, ciclesonide could accelerate the assembly in a concentration-dependent manner. Molecular simulation suggested that ciclesonide could bind to NTD-CTD interface of adjacent protomers in the CA hexamer via H67 and L211 residues. These results indicated that ciclesonide was a potential moderator of HIV-1 capsid assembly.

Key words: ciclesonide, capsid assembly, C-terminal domain, human immunodeficiency virus 1, homogeneous time-resolved fluorescence