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Napolitano, V. ; Dabrowska, A.* ; Schorpp, K.K. ; Mourao, A. ; Barreto-Duran, E.* ; Benedyk, M.* ; Botwina, P.* ; Brandner, S. ; Bostock, M.J. ; Chykunova, Y.* ; Czarna, A.* ; Dubin, G.* ; Fröhlich, T. ; Hölscher, M.* ; Jedrysik, M.* ; Matsuda, A.* ; Owczarek, K.* ; Pachota, M.* ; Plettenburg, O. ; Potempa, J.S.* ; Rothenaigner, I. ; Schlauderer, F. ; Slysz, K.* ; Szczepanski, A.* ; Greve-Isdahl Mohn, K.* ; Blomberg, B.* ; Sattler, M. ; Hadian, K. ; Popowicz, G.M. ; Pyrc, K.*

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

Cell Chem. Bio. 29, 774-784.e8 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Covid-19 ; Pl(pro) ; Sars-cov-2 ; Acriflavine ; Coronavirus ; Drug Repurposing ; Protease ; Protease Inhibitor ; Structural Biology
ISSN (print) / ISBN 2451-9448
e-ISSN 2451-9456
Journal Cell Chemical Biology
Quellenangaben Volume: 29, Issue: 5, Pages: 774-784.e8 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Massachusetts
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
Institute of Molecular Toxicology and Pharmacology (TOXI)
Institute of Medicinal Chemistry (IMC)
Grants Ministerstwo Edukacji i Nauki
Narodowe Centrum Nauki
Bayerische Forschungsstiftung
Fundacja na rzecz Nauki Polskiej
AstraZeneca
EU-Horizon2020