The entry inhibitor DS003 (BMS-599793): a BMS-806 analogue, provides superior activity as a pre-exposure prophylaxis candidate.

ABSTRACT:

Objective

Small molecule inhibitors able to bind to gp120 and prevent CD4+-induced HIV-1 envelope conformational change provide an important class of inhibitors. Currently, only Fostemsavir is approved for HAART, which makes this class of inhibitors attractive candidates for prevention. We assessed the activity of DS003 (BMS-599793), an analogue of BMS-378806, in different mucosal tissues and elucidated its mechanism of action.

Design

Preclinical analysis was performed with human mucosal tissue models as surrogates of in-vivo activity.

Methods

Antiviral efficacy of DS003 was assessed in mucosal tissue explants (ecto-cervical, penile and colorectal) and in trans-infection models (co-cultures of dendritic or mucosal migratory cells with CD4+ T cells) with several dosing

SUBMITTER: Herrera C 

PROVIDER: S-EPMC8416713 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature