The Compound AT13148 Targeting AKT Suppresses Dengue Virus 2 Replication.

Abstract

Background: Dengue virus (DENV) infection, caused by serotypes DENV 1-4, represents a significant global public health challenge, with no antiviral drugs currently available for treatment. The host Protein kinase B (AKT) signaling pathway is crucial for DENV infection, presenting a potential target for antiviral drug development. Objective: This study aimed to evaluate the antiviral activity of kinase inhibitors that target the AKT pathway, focusing on the compound AT13148. Methods: A mini-screening was conducted to identify kinase inhibitors with antiviral properties against DENV-2. The effects of AT13148 on viral RNA replication and translation were assessed in a dose- and time-dependent manner following DENV-2 entry. The mechanism of action was further investigated by evaluating the impact of AT13148 on AKT kinase activity and phosphorylation status. Results: AT13148 exhibited potent antiviral activity against DENV-2, significantly inhibiting viral RNA replication and translation post-entry. The compound was found to inhibit AKT kinase activity through hyperphosphorylation. Conclusion: The findings indicate that AT13148 effectively targets the AKT pathway, demonstrating potential as an antiviral therapeutic against DENV-2 by interfering with the virus's post-entry processes. Further in vivo studies are warranted to assess the efficacy of AT13148 in controlling DENV infection.