Title:	Computational studies of viral enzymes
DNr:	NAISS 2025/22-121
Project Type:	NAISS Small Compute
Principal Investigator:	Flavio Ballante <flavio.ballante@ki.se>
Affiliation:	Karolinska Institutet
Duration:	2025-01-31 – 2026-02-01
Classification:	30103
Keywords:

Abstract

Direct-acting antivirals are urgently needed to combat future pandemics caused by Zika or Dengue viruses. By combining crystallographic fragment screens with computational chemistry and biochemical assays we aim to rapidly identify novel inhibitors targeting flaviviruses. We will perform in silico screening for hit-to-lead optimization of fragment hits that have been identified from a crystallographic screen and confirmed by in vitro assays. Driven by the experimental results we will perform ultra large virtual screening campaigns to prioritize new compounds. We will apply molecular docking, similarity-based searches, and machine-learning approaches. Candidates from the simulations will be experimentally tested in crystallographic screens and bioassays.