Development of a SAR-Guided Virtual Screening Strategy to Identify Allosteric Inhibitors of Zika Virus NS2B/NS3 Protease

Identifier:  TFG:9073

Handle: https://hdl.handle.net/20.500.11797/TFG9073

Authors:  Montano Hernández, Judith

Abstract:
Zika virus remains a global health concern due to its reemerging risk, severe complications, and lack of vaccines or antiviral therapies. The NS2B/NS3 protease is an attractive target, as it processes the viral polyprotein. However, direct active-site inhibition has been challenged by poor inhibitor permeability and active-site similarity to human serine proteases. To address this, an allosteric inhibition strategy was pursued, aiming to stabilize the inactive conformation of the protease. Structure-activity relationships of known allosteric inhibitors were analyzed and integrated into a virtual screening workflow. This approach yielded twenty potential allosteric inhibitors for future experimental evaluation.