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

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 PotempaIna Rothenaigner, Florian Schlauderer, Klaudia Slysz, Artur Szczepanski, Kristin Greve-Isdahl Mohn, Bjorn Blomberg, Michael Sattler, Kamyar Hadian, Grzegorz Maria Popowicz, Krzysztof Pyrc

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish
Pages (from-to)774-784.e8
JournalCell Chemical Biology
Issue number5
StatePublished - 19 May 2022
Externally publishedYes


  • COVID-19
  • PL
  • SARS-CoV-2
  • acriflavine
  • coronavirus
  • drug repurposing
  • protease
  • protease inhibitor
  • structural biology


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