Title:	Study of interactions between small molecules and and flavivirus viral proteases
DNr:	NAISS 2025/22-765
Project Type:	NAISS Small Compute
Principal Investigator:	Dario Akaberi <Dario.akaberi@imbim.uu.se>
Affiliation:	Uppsala universitet
Duration:	2025-05-22 – 2026-06-01
Classification:	10606
Keywords:

Abstract

Vector-borne flaviviruses like dengue, West Nile, yellow fever, Japanese encephalitis, tick-borne encephalitis, and Zika virus are important human pathogens responsible for a high health and economic burden worldwide. Despite the urgent need, no antivirals for the prevention or treatment of flavivirus infections and mitigation of future outbreaks are currently available. While flaviviruses protease are structurally conserved and compounds with broad spectrum activity have been reported in the literature, most of the research focuses on the study of inhibitors targeting one virus at a time. Pan-flavivirus inhibitors would be extremely valuable as they would allow the treatment of several flavivirus infections with just one pill. This project aims to study the interaction of different protease inhibitors in complex with proteases from several flaviviruses. Compounds will be docked to the available structures of NS2B/NS3 proteases from different flaviviruses and the binding stability over time and affinity will be evaluated from analysis of molecular dynamics simulations trajectories.