Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses

authored by
Valeria Napolitano, Agnieszka Dabrowska, Kenji Schorpp, André Mourão, Emilia Barreto-Duran, Malgorzata Benedyk, Pawel Botwina, Stefanie Brandner, Mark Bostock, Yuliya Chykunova, Anna Czarna, Grzegorz Dubin, Tony Fröhlich, Michael Hölscher, Malwina Jedrysik, Alex Matsuda, Katarzyna Owczarek, Magdalena Pachota, Oliver Plettenburg, Jan Potempa, Ina Rothenaigner, Florian Schlauderer, Klaudia Slysz, Artur Szczepanski, Kristin Greve-Isdahl Mohn, Bjorn Blomberg, Michael Sattler, Kamyar Hadian, Grzegorz Maria Popowicz, Krzysztof Pyrc

The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.

Centre of Biomolecular Drug Research (BMWZ)
Institute of Organic Chemistry
External Organisation(s)
Helmholtz Zentrum München - German Research Center for Environmental Health
Jagiellonian University
Ludwig-Maximilians-Universität München (LMU)
Justus Liebig University Giessen
Technical University of Munich (TUM)
Haukeland University Hospital
Cell Chemical Biology
Publication date
Publication status
Peer reviewed
ASJC Scopus subject areas
Biochemistry, Molecular Medicine, Molecular Biology, Pharmacology, Drug Discovery, Clinical Biochemistry
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Electronic version(s) (Access: Open)