A Broad-Spectrum Antiviral Molecule, Protoporphyrin IX, Acts as a Moderator of HIV-1 Capsid Assembly by Targeting the Capsid Hexamer.

ABSTRACT: The capsid protein (CA), an essential component of human immunodeficiency virus type 1 (HIV-1), represents an appealing target for antivirals. Small molecules targeting the CAI-binding cavity in the C-terminal domain of HIV-1 CA (CA CTD) confer potent antiviral activities. In this study, we report that a small molecule, protoporphyrin IX (PPIX), targets the HIV-1 CA by binding to this pocket. PPIX was identified via in vitro drug screening, using a homogeneous and time-resolved fluorescence-based assay. CA multimerization and a biolayer interferometry (BLI) assay showed that PPIX promoted CA multimerization and bound directly to CA. The binding model of PPIX to CA CTD revealed that PPIX forms hydrogen bonds with the L211and E212 residues in the CA CTD. Moreover, the BLI assay demons

SUBMITTER: Zhang DW 

PROVIDER: S-EPMC9927277 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature