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A host-centric morphological profiling approach to identify repurposed antiviral drugs.

Created on 19 Jul 2026

Authors

Elin Asp, Jonne Rietdijk, Marianna Tampere, Hanna Axelsson, Duncan Njenda, Swapnil Potdar, Adelinn Kalman, Polina Georgieva, Maris Lapins, Flavio Ballante, Alicia Soler, Martin de Kort, Tero Aittokallio, Andrea Zaliani, Maria Kuzikov, Philip Gribbon, Donald Lo, Jordi Carreras-Puigvert, Brinton Seashore-Ludlow, Ola Spjuth, Päivi Östling

Published in

iScience. Volume 29. Issue 8. Pages 116673. Aug 21, 2026. Epub Jul 10, 2026.

Abstract

Antiviral drug discovery has traditionally targeted viral proteins, while host-directed strategies remain underexplored. We present a systematic drug repurposing strategy that uses morphological profiling to identify host-targeting antivirals. Using cell painting, we demonstrate that SARS-CoV-2 infection can be accurately determined from the morphological profile of virus-infected cells. Moreover, morphological features reveal how host cells respond to viral exposure, offering insights into antiviral activity, host-cell health, and putative mechanisms of action of the compounds. Screening 5,275 repurposable compounds, we identified candidates that reversed the infected phenotype, including ones not detected by conventional cytopathicity and antibody-based assays. After deprioritization of confounding phospholipidosis, we present 74 hit candidates, including unreported compounds targeting host processes implicated in viral infection. This adaptable and scalable platform is suited for diverse viruses and cell systems. We provide a resource of open-access screening data, images, and analysis pipelines to advance antiviral discovery and pandemic preparedness.

PMID:
42472122
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.

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