Systematic computer-aided disulfide design as a general strategy to stabilize prefusion class I fusion proteins.

ABSTRACT: Numerous enveloped viruses, such as coronaviruses, influenza, and respiratory syncytial virus (RSV), utilize class I fusion proteins for cell entry. During this process, the proteins transition from a prefusion to a postfusion state, undergoing substantial and irreversible conformational changes. The prefusion conformation has repeatedly shown significant potential in vaccine development. However, the instability of this state poses challenges for its practical application in vaccines. While non-native disulfides have been effective in maintaining the prefusion structure, identifying stabilizing disulfide bonds remains an intricate task. Here, we present a general computational approach to systematically identify prefusion-stabilizing disulfides. Our method assesses the geometric constrain

SUBMITTER: Gonzalez KJ 

PROVIDER: S-EPMC11303214 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature