Automated Design by Structure-Based Stabilization and Consensus Repair to Achieve Prefusion-Closed Envelope Trimers in a Wide Variety of HIV Strains.

ABSTRACT: Soluble envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit neutralizing responses against HIV-1 strains closely related to the immunizing trimer. However, to date such stabilization has succeeded with only a limited number of HIV-1 strains. To address this issue, here we develop ADROITrimer, an automated procedure involving structure-based stabilization and consensus repair, and generate "RnS-DS-SOSIP"-stabilized Envs from 180 diverse Env sequences. The vast majority of these RnS-DS-SOSIP Envs fold into prefusion-closed conformations as judged by antigenic analysis and size exclusion chromatography. Additionally, representative strains from clades AE, B, and C are stabilized in prefusion-closed conformations as shown by negative-stain electron microscopy, and

SUBMITTER: Rawi R 

PROVIDER: S-EPMC7714614 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature